Title The Chemistry on Diterpenoids in 1977. Part-I ...Stereoselective total synthesis of rac-podocarpic acid (1) was published.2' Key step of the synthesis consists of concomitant

Title The Chemistry on Diterpenoids in 1977. Part-I

Author(s) Fujita, Eiichi; Fuji, Kaoru; Nagao, Yoshimitsu; Node, Manabu

Citation Bulletin of the Institute for Chemical Research, KyotoUniversity (1978), 56(3): 111-138

Issue Date 1978-07-31

URL http://hdl.handle.net/2433/76775

Right

Type Departmental Bulletin Paper

Textversion publisher

Kyoto University

Bull. Inst. Chem. Res., Kyoto Univ., Vol. 56, No. 3, 1978

uuuuuiuwunmumnnw

Review

The Chemistry on Diterpenoids in 1977. Part-I

Eiichi Funk,* Kaoru Fuji, Yoshimitsu NAGAO, and Manabu NODE

Received May 23, 1978

I. INTRODUCTION

This is one of a series of our annual reviews') on diterpenoids chemistry. The classification of the compounds is the same as that adopted in our reviews since 1969.

This review covers the literatures published between January and June 1977.

II. PODOCARPANE DERIVATIVES

.20 II 11 13 9 H 14-

2 I to 3 45

11 1.8 Podocarpane

Stereoselective total synthesis of rac-podocarpic acid (1) was published.2' Key step of the synthesis consists of concomitant reduction, deoxygenation, and stereoselective alkylation of vinyl ester 2 by treatment with lithium metal in liquid ammonia and dimethoxyethane followed by methyl iodide. This method provides a general synthetic

procedure for the construction of podocarpane type natural products.

oHoMe

PI Me0cH20Si!.11101-41r .

Holccol Me

(1)(2)

Baeyer-Villiger oxidation of 7-oxocompounds 3 and 4 and ring-B cleavage followed

* X± X , Rj A jE, } : Laboratory of Physiological Activity, Institute for Chemi- cal Research, Kyoto University, Uji, Kyoto-Fu 611, Japan.

(111)

E. FuJmTA, K. Fuji, Y. NAGAO, and M. NODE

by ring-B recyclization afforded 11, 14-dimethoxypodocarpic acid derivatives 5 and 6 respectively. The reaction sequence is outlined in Chart 1.8>

oMeoMeoMe

®®me0 IMO , --> IP . — —i • OMe_ _—, Ole®ft Me

R (3)R=Me(5) 1 fre

(4) R = co.ole(6) R = coLMe

Chart I

Rearrangement of the epoxide 7 with boron trifluoride etherate gave compound 8 in

32% yield.'" The synthesis of (—)-podocarpic acid from (+)-dehydroabietic acid was

reviewed' Effects of 54 podocarpane derivatives on the growth of rice and barnyard

grass seedlings were investigated."

oNoff

® °opl 00croilip H 02C -.

(7) (8)

III. LABDANE DERIVATIVES

16 t1 ' H

a0II13 io i lip a to>4 ,c

3 4 5:

: H

14 18

Labdane

A new diterpene, 4-epiisocommunic acid (9) was isolated as the methyl ester from Callitris rhomboidea.7> - The structure 10 of a new diterpene isolated from Metasequoia

glyptostroides was determined mainly by 13C NMR spectroscopy.8> New diterpenes, dendroidinic acid (11) and hebeclinolide (12), were isolated from Ageratina dendroides and Hebeclinium macrophyllum respectively."

Five new labdane diterpene oxides, jhanol (13), jhanol acetate (14), jhanidiol (15),

jhanidiol-18-monoacetate (16) and jhanidiol diacetate (17), were isolated from Eupa-torium jhanii.'e> Coleus forskohlii was found to contain five diterpenoids, 18-22, three of which (20-22) display blood pressure lowering and cardioactive properties.")

(112 )


MQ

Me,,e1-14 ~C0'Ha IH co/ 1;:ti.:CO2H~ HAc0~r>0

Ho Co1HH

(9)(10)(I l )(12)

R'....~/R' oGOH 00

H®191k®:H H3•.0 'cH,~oH HO g2oeBrH

(13) Ri=R'=H(18) R'=R2=le=H, R3=Ac(23)

( 14) R'=H, f'-,.'A, (19) R'=R'=R3=R``=H

( 15) RI=. OH, R'= H (20) R1= Re= 0H, R a H, t = A,

( 16) R'= oH. R'.--Ac. (21) /V= x*-- RI= R3=H

( 17) R'=OAc,R'=Ac (22) R'=R"=OH, R2-Ac,Rg-N

A brominated diterpene, isoapsin-20 (23) was isolated from a sea fish, Aplysia

kurodai.121 New diterpenes 24-28 from Austroeupatorium inulaefolium,13) 29 and 30 from

Ballota nigra14,15) and 31 and 32 from B. rupestris151 were isolated.

oR .7z:C.-R

off0 •Rz0,of

I-1•OHH off

(24)(25) R'=H,R'-OH (27) R=0 (26) R'=oH,R'=H (28) R=H2OH

cit,..011'..tiI 1I 1 ,o.'0Ac.R. 0a o kH

HMV 1.HOHro/-"• (29)(30) (31) R="1 A.,

(32)R= 0

Cationic cyclizations of 33, 34, and 35 derived from manool (36) did not result in the hoped-for biogenetic-type strobane synthesis, but yielded 37, 38, and 39, respectively as well as a phyllocladane derivative 40 in the case of 35.16)

Oxidation of 34 with modified Collins reagent gave 41 (38%) and epoxyketones,

42 (17. 3%) and 43 (31%), which would be useful for effecting the 1, 3-transposition of oxygen and for carrying out mixed aldol condenzations. This oxidation was successfully applied to manool (36) giving rise to the higher yield of the products 44 (69%) and

(113)

E. FuJITA, K. Fuji, Y. NAGAO, and M. NODE

45 (21%).1~) Four tobacco diterpenoids 46-49 were derived from (12Z)-abienol (50).18)

\H~

off 00 (33)(34) R=H(36)(37)

(35) R =Ac

e„.eorie"tl oA. go*

•

(38)(39)(40)(41)

o°

Cf:5-1° HH 040 CI:9(0.10 (42)(43)(44)(45)

~s0off0 RI I-"R2

,®s®s® 00off ?N :H

(46) (47)(48) RI=Me, R`=CH=cHz (50)

(49) R1=cH=cHz, R=Me

IV. CLERODANE DERIVATIVES

.20 1 H ;II 13

N I a I 10'?, 8 141. s 3 16 5. 6 ?

H Is Clerodane .. .

A new cis-clerodane-type diterpene, linarienone (51) was isolated from Linaria

japonica.19) The structure of teucrin H 1 (52) isolated from Teucrium hyrcanicum was determined by spectroscopic means.20)

(114)


OAc 0' •o,

0HCH08M¢Ho '•, Me H

0 0 (51)(52)

V. PIMARANE AND ISOPIMARANE DERIVATIVES

w

3`)c11 20U y

2.) )oHa)S~ib 1"1 s~'~5 HN

19 ) PimaraneIsopimarane

Pimara-8, 15-diene (53) has been isolated from Trichothecium roseum. Its biosyn-thesis is described.21) The structures of two new metabolites, virescenosides D (54) and H (55), isolated from the fungus Acremonium Iuzulae (Fuckel) Gams, were elucidated22) Reinvestigation of annonalide isolated from Annona coriacea by X-ray analysis confirmed the stereochemistry to be as shown in 56.23)

0 eH,PH

s,1. HO 00HO'00

NH

( 53 )Ro( 54 ) R=CHOo0 H( 55 )R= cHaoH(56 )

H

A search for growth and germination inhibitors in rice husk revealed three diter-

penoids, ineketone (57), momilactones A (58) and B (59) 24) The latter two were also isolated from ultraviolet-irradiated dark-grown rice coleoptiles as the major phytoalexins.25)

Chemical and physical properties of momilactones A (58) and B (59) were studied in

H111 4a ' •I-100WIHoo

;oHo00 ( 59 )

(57)(58)

( 115 )

E. FuJiTA, K. Fuji, Y. NAGAO, and. M. NODE

detail.zs>

Hypocholesterolemic action of tricyclic diterpenoids in rats involving the pimarane- type has been investigated.27>

VI. ABIETANE DERIVATIVES

11 >s

20 I> 11 (3' j6 9 H

z,> >c H 8 3 5`9

H 19 >b

Abietane

The structure of coleon L(60) isolated from Coleus somaliensis was elucidated unambiguously, which allowed to revise the structures of coleon H, I and I' to be 61,

62, and 63 respectively.28) The structure of coleon K was also revised to 64, based on the fact that coleon L was easily transformed into coleon K on standing in solu- tion 28> Coleons S (65) and T (66) were isolated from Plectranthus caninus.29>

R3R3 off cH:

HooffcH, `"'R'HOcNR:

F

0H

RIOIIPPW 0R>0OH on4N •

(60) R'=Ac, R' 0H, R3=0Ac (62) R1-=Ac, R'=H, R3=oH

(61) R'=Ac. R'= H. R3=oH (63) R'=cUO, R7=11, R3= off

(65) AI= R3°R3_H(64) R'=Ac,R''=oH, R30,4c (66) R'=R'=R3=H

The structures of three diterpenoids from Coleus barbatus have been determined. They are barbatusin (67), 319-hydroxy-3-deoxybarbatusin (68), and cyclobutatusin (69).

The structures of 67 and 69 were established by X-ray diffraction analysis.3>> Irradia- tion of barbatusin (67) produces dehydrocyclobutatusin (70), whose structure was deter-

mined by X-ray methods.>'>

O DAcOAcOHOAc Ho ''H•

R •I'OH'o OAcHOH0/''OH OAc' . H OAc (67) R=0(69)

(68)R=d•H,p-oH(70)

(116 )


rac-Callitrisic acid (71) was synthesized through the key intermediate 72 by the

same method applied to the synthesis of rac-podocarpic acid described in charpter 1I.2)

Abietic acid afforded 73 on treatment with bis(2-hydroxy-l-naphthyl)disulfide at 200°,

whereas toluene-3, 4-dithiol at 250° gave mainly the disproportionation products 74 and

75.32)

MeocHso owe

R' R' Co. Me.0 ojH

(71)Re= HeRz=CO=H(72)(73)(74)

(75) R'=COZH, R=We

Oxidation at the C-11 position of methyl 12-hydroxyabieta-8,11,13-trien-18-oate

(76) and ferruginol (77) were successfully carried out using benzoyl peroxide, and the resulting phenols 78 and 79 were further converted into taxodione (80), royleanone

(81), cryptojaponol (82), and methyl 11-hydroxy-12-methoxy-7-oxoabieta-8,11,13-trien-18-oate (83) 33)

Kt oR'~ Ho0offNo°Me

• H R3HO:il=.H

(76)R'=R=H, R=CozMe (80) (81)M2

(77)R1=R=H,R3=Me(82) R= (83) R = co,.Me

( 78) R'=copk,R=oH, R?=CO.Me

( 79 ) R'= copk, R =aH, R 3=Me

A convenient synthesis of rac-ferruginol (77) and rac-sugiol (85) has been published.3a)

The outline is shown in Chart 2. rac-Taxodione (80) has been synthesized from the

intermediate 84 using benzoyl peroxide oxidation as mentioned above as shown in Chart

3.

off

tomeoMe :o® oMe 110:1( off

C/\Ho+---->)ii— et cI,

H

o (84):r+

(85) Chart 2

(117 )

E. FuJiTA, K. Fug, Y. NAGAO, and M. NODE

01QOMe()cork0 otiH.

II--0--1*!--- --) gie-' oip off: HHOHHO

(84)(80) Chart 3

Ozonolysis of phenolic dehydroabietic acid derivatives was investigated. Direction of

cleavage of the aromatic ring by means of ozonolysis was found to be affected by the

substitution pattern of hydroxyl groups in the aromatic ring 35) A variety of sulfonamides

86 were obtained in 75-86% yields by amidation of the corresponding chlorosulfonyl

derivatives with RNH3 3s' Epidioxide 87 gave 88 and 89 on remote oxidation with ferrous

sulfate.3) Compound 90 was obtained from 87 by stirring overnight with silica gel.33>

The mechanism for the formation of 92 and 93 upon irradiation of 91 in benzene has been investigated by spectroscopic and by quenching and sensitization methods.39'

rumsoffON

e.10e Jo 'coaMe .COsMeCO}M¢Lo}M~

(86) (87) (88)(89)

04.,oMe~oMe /oMe

off4mr0I^,,* I^/1//11/0~o H Co

,Me. CO,MeCOaMe *Co2, Me

(90) (91) (92)(93)

0

AMo• ...*

COsH H i HOHC~.H

(94)610 (95) (96)

Imide 94 was prepared from maleopimaric acid by ammonolysis and subsequent

cyclization.°0) Potassium triphenylmethide was found to be effective base to prepare

enolate anion. Thus, methylation of aldehyde 95 using this base and methyl iodide

afforded the alkylated compound 96 in 97% yield.91'

The synthesis of (—)-podocarpic acid from (+)-dehydroabietic acid was reviewed

in Japanese.') Hypocholesterolemic action of abietane derivatives in rats has been report-

ed.a7p

(118)


VII. TOTARANE DERIVATIVES

20 1~ Ii i3 9: H A 10 H.. 8 •' IB

3 4 5 616

H

19 18 Totarane

Maytenoquinone (98) , dispermol (99) , and dispermone (100) were synthesized from

19-cyclocitral (97) as shown in Chart 4.42)

OMeorle

OMe 14 Megal 0M oMe Op sue cute.,oN`•.o

(97) or9efo meI 0 oneY-cral OH..OH

• OPs p;1-1 '

HH

(100)(99)0(98) Chart 4

Hypocholesterolemic action of totarane derivatives in rats has been reported?")

VIII. CASSANE DERIVATIVES

1s

20 II Ia 13 '''''N`16 H 14

2. r17 3lip

4

N_

19 14

Cassane

No reports were published in this period.

(119 )

E. FuJrrA, K. Fuji, Y. NAGAO, and M. NODE

IX. KAURANE DERIVATIVES

,~:H 20 .I>3

a > )DH g ilip I 3+h56

N

(1 11 Kaurane

The isolation and structural elucidation of three ent-kaurane diterpenoids (101-103) from the liverwort Jungermania infusca were published.43) From the liverwort Junger-mannia shaerocarpa, ent-lla-hydroxykauren-l5a-yl acetate (104), ent-lla-hydroxy-kauren-15-one (105), and ent-kaurene- I la, 15a-diol (106) were isolated. Their structures were confirmed by X-ray analyses.44,46>

RRHo litikalk~~to•ao eaoffP

H.NOAe

(101)(102) R = H (103) R = H (104)

(105) R=oH (106) R=oH

It was shown that Austroeupatorium inulaefolium contains three known kaurane

type diterpenes (107-109) besides five new labdane type diterpenes.13> The roots of

Polymnia fructicosa and P. pyramidalis were found to contain kaurenic acid (107) and

the derivatives 109 and 110. The aerial parts of the latter plant also contains 107.46)

NQ

N~~if Oc ;H ,:Nn RCoiH 0 Me

(107) R = co=H (108)(110) (

109) K = cHA0H

(122) K = cHO

From the roots of Wedelia triloba, several new kaurenic acid derivatives (111-114) were isolated together with the known diterpenes (107 and 115) . From the aerial

parts of W. triloba, 107, 113, 115, 116, and 117 were isolated. From the roots of W. helianthoides, 107, 114, 115, 118, and 119 were obtained. From the roots of W. gran- diflora, 107, 108, 109, 114, 115, 118, 120, 121, and 122 were isolated. From the aerial

parts of the same plant, 107, 109, and 115 were isolated.47>

(120)


(111) R1=-0-C--?-71e, , R"= R'=N 0 MeM.

a Me ~~ ISOr

oHRH -covi

(114) A1= H, R¢"ON. f3=-o"1' e (115) 0 Me

(116) R'= -0-c-cu=cMe3 ow

R' .~(117)R1 = H,R'=-o-I~`ccHs o N H MQ

co,H(118) R', H, R`=-01-1Cle o MeH 11 Me

rte2o.H o (119) )'=p, H

o(123)

(120) R'= H, R1=-o-i -cH=cMes Me (121) its =II, o H"'e

0

A new diterpene carboxylic acid, perymenium acid (123) was isolated from the roots of Perymenium ecuadoricum together with four known diterpenoids, 107, 108, 109,

and 122.98' The structures including absolute configurations of two new diterpenes isolated from

Porella densifolia were elucidated as ent-18-hydroxykauren-15-one (124) and ent-18-hydroxykauran-15-on (125) in combination of chemical reaction and spectroscopic analysis.4) Inflexin (126) isolated from the leaves of Isodon inflexus was found to exhibit cytotoxicity, insect antifeedant and other bioactive properties. The structure of infilexin was determined by spectroscopic and chemical methods.5) From seeds of Cucurbita

pep, a new kaurenolide was isolated51> and the structure was elucidated to be 127.52)

off

®i OOA .0/~o,~ HOHHC•':HHONic•tHN0off•

0 (124)(125)(126)(127)

The structure of cofaryloside, a so far unknown glucoside from green coffee-beans, was determined to be ent-B-D-glucopyranosyl 9a, 16p, 17-trihydroxykauran-19-oate

(128) •53) From the leaves of Stevia rebaudiana; three new sweet glycosides, named rebau-dioside-C, -D, and -E, were isolated. The structure 129 was assigned to rebaudioside-C

(121)

E. FUJITA, K. Fug, Y. NAGAO, and M. NODE

by the use of 13C NMR as well as chemical evidence.541 Chemical and spectroscopic examinations led to the presentation of the formulas 130, 131, and 132 for asebotoxin-VI, -VIII, and -IX isolated from the flowers of Pieris japonica, respectively.55) In the

report about 13C chemical shifts of isoprenoid-j3-D-mannopyranosides, steviol-monoside

(133) was described.5) The mass spectrum of (17-13C) 13p-kaur-16-ene (phyllo-cladene) was examined and the percentage retention of label was calculated using a

computer program.5 )

Ilkop a cT\~Rh cH3oti t Ho

00- 0 off•~ H O NI*H H t ox tOH, COxIT

OW OR'OR3oH (128)(129)

(130) R'_R3-H, R =coEt

H HOC7 (131) R~= Ac or COEt, R'-H,

HOR3= CoEt or Ac

:Ho,0 • off bR' 01pH: H =13-gr.lucopyrano5yi 02.11

(132) or Ac or CoEt(133) Rk = oc-rhaynnopyranosyl

R2= COEt or Ac

It was found that host-plant resistance to the sunflower moth (Ho moeoso ma electel-luin) is caused by ent-kaur-16-en-19-oic acid (107) and trachyloban-l9-oic acid.58)

The conformational analysis of the E and F rings of atisine, veatchine (134), and related alkaloids was investigated. The 13C NMR analysis of related alkaloids did not indicate the existence of two conformers (135 and 136) and confirmed the existence of C-20 epimers (137 and 138).5"

eMej ..0..tie1.00 offit4e,1Nxo oU=:oN\L /LOH"( (134)(135) (136) (137)(138)

Several grandiflorenic acid derivatives 139a f, 140, 141, and 142 were prepared.60

Acid hydrolysis of stevioside (143) was carried out under a mild condition with 0. 4 a/o HC1 in aq . methanol at reflux for 5 hours, and steviol, the genuine aglucon which

had been only obtained by enzymatic hydrolysis of stevioside, was afforded in 49%

yield.6) The quantitative analysis of stevioside by the application of Carr-Price reaction was examined.")

Reactions of alkenes with thallium(I) acetate and iodine chloride were reported. In

(122)


,y, Ho

Ho.,,

likt Iii S,.. H~off

•,62 .0 (140) _J'"o RHo

(139)a Ri=a-Plel'oN, le.--co,.H

C151'— i KI=d-oH,p-cH,oH,R=co:H00 cR'=d-H, p•cHjoe,itco,HtH= H

d R'=o, R''= coLH co:H (141)iO HOp(143)

H

f i.'=d-H, f3•cH,oH, R=cH,oHOH HO . H''OH off io,H(142)

this work 13p-kaur-16-ene (phyllocladene) (144) was converted to three acetates,

145 (59%), 146 (21%), and 147 (20%).65)

H Illip, cN1I OPW cH,oA~ ,•.OAc~®Ao •

(144)(145)(146) (147)

Treatment of ent-17-norkauran-16-one (148) with thallium(III) nitrate in acetic acid

gave several oxidative rearrangement products, 149, 150, 151, and 152. The diterpene skeleton of those rearrangement products, ent-9(8-515aH)abeo-kaurane (153), was

synthesized as shown in Chart 5.641

1. .. •00 ib ''PtC C.

7-n

®/ 0:411kIOW/GA

RH (148)(149) R -'14(151) K=H

(150) R-OAc(152) R=Ac

Oar "--1..--4 di 11 il-b-ll'4 Illie .ti. I.." 4411Vil H:H:H

(149)(153) Chart 5

The stereochemistry of the photoaddition of allene to hydroindenal 154 was proved

by conversion of its product 155 into steviol methyl ester (156) and isosteviol methyl

(123)

E. FuJrrA, K. FuJI,Y. NAGAO, and M. NODE

ester (157). The sequence is shown in Chart 6.65)

4ppcH0E 1110CHsoMs

H C92= C =cHL H:) MsclH • co2>"1e f v, -78' 'CO,.Meeo.r1e

(154)(155)

OHMeoMs

—~1 ~- 4111 APIs

,9,R= H•0a OaP1'c o:lit H

(156)(157)HCI CosNle62214 Chart 6

In experiments directed towards the total synthesis of fujenoic acid (158), the 2-(2-furyl)-6-oxobicyclo(3, 2, 1)octane-l-carboxylate (159) was prepared as a key intermediate. (Chart 7) Furthermore, in investigation of the model transformation into ring A of fujenoic acid, the model compound 160 was effectively converted into 161 as shown in Chart 8.66)

9t4a,AcoMef2)tBuoK>T"LiIPgr.f'' c10 co,..co,.Me esc... MtV"' H

s `CO,H CoaMe°O%'0 fo1Me(159) o1)'0 (158) Co a2 .Luryl J

Chart 7

OTsoAc403-Py;,t-t3u0K,Mei ~''co,MeNoHoc02Me0COxMe CozMe

[o,MeCOztieeo,MeCovle

(160)(161)

Chart 8

Total synthesis of gibberellins A15 and A37 using a kaurane derivative as the relay

compound and chemical conversion of gibberellins A>> and A37 from enmein were

reported.67> (See Section XI.)

X. BEYERANE DERIVATIVES

11 '1

LO° n• y 4j

2.1 to Ne • is 3 S 6 >

. N

19 IS Beyerane

(124)


Carbon-13 NMR spectra of stachenol (162) and related derivatives were published.")

Total synthesis of isosteviol methyl ester (157) was reported.65' (See Section IX.)

HO. - (

162)

XI. GIBBERELLANE DERIVATIVES

ao H

2. to 3y,K~u•H H 19 Ifl 9I7

Gibberellane

Gibberellin A17(163) was identified by GC-MS from both immature and mature

seeds of Pyrus communis. Immature seeds also contained gibberellins A25(164) and A45

(165), and two presumed mono-hydroxylated derivatives of gibberellin A45f one of which was tentatively identified as 3 p-hydroxy-gibberellin A45 (166).69' Isolation of three new

gibberellins A39, A48i and A49 together with a new kaurenolide was reported51' and their structures were shown to be 167, 168, 169, and 127, respectively.52>

Ho1C H0 HHOC HOHH0oiiiR'(ZHHOHHN0H •R3 CY1IR H0 c CO=HCOaHHOCCO,,HCoH

za

(163) R=OH (165)R=H (167)(168) R'=oH, RC--H

(164) R=H (166)R=OH(169) R'=H.R'=oH

Effects of several hydrotluorene derivatives transformed from abietic acid on the

growth of rice and barnyard grass seedlings were investigated.70' The negative ion mass spectra of 170 and ten C19 gibberellins were discussed and compared with the positive

ion mass spectra.71' Four new fluoro-gibberellins (171, 172, 173, and 174) containing

bridgehead fluorine atoms were prepared by the fluorination of esters of gibberellins

with 2-chloro-N, N-diethyl- 1, 1, 2-tritluoroethylamine, followed by de-esterification.72'

Aminolysis of a gibberellin anhydride 175 with esters of amino acids followed by

H0 NFO H0N0 H rHF00..F.lp 1Fcos F /HHHi

MeMeco,H CO,HC0JHR coaN R

(170)(171) (172) (173) R=01-H,3-Me (174) 1(=0(-HtMe andand

g= oc-Me,3-H R=oc-Me,t-H

(125)

E. FuJrrA, K..FujI, Y. NAGAO, and M. NODE

demethylation with lithium-n-propyl-mercaptide as well as a direct fission of the anhy-

dride with alkali salts of amino acids led to gibberellin-aminoacid-conjugates (176).7' The 0(3)-(3-D-glucopyranosides of gibberellins A1, A3, and A4 (177, 178, 179) and the

0(13) -p-glucopyranosides of gibberellins A1, A3, and A5 (180, 181, 182) were synthesized

by means of the Koenigs-Knorr reaction. In addition to these monoglucosides the

gibberellin A3-0(3, 13)-di-p-D-glucopyranoside (183) was synthesized.74)

O H

HO C•S offors 0 HHooff H Co 2H

I 0 d-cH-R

Grbberefltn A3-5ystem(a')co,H Enbberell^n A,-system (1.2-CT /13-5ystem (a')

saturated)CTA,-5ysleon (,,2-saturateA)

(175)(176)

0 HO H 0 H0 H Y

RIO®.ORZ,WWOreOw~H1~~04K0ErH COLNCO2H _ C01HCOQH

(177) RI= t . R;H (178) R'=CT, R2=H (179)(182)

(180 IZ'cH. R2=CT (181) R'=H, R2z Cr CT =(3-D11ucopyranosyl

(183) R'=R"=CT

The 0(13) -13-D-glucopyranoranosyl-allogibberic acid 0-p-D-glucopyranosyl ester

(184) and 0(13)-S-D-glucopyranosyl ester (185) were synthesized from allogibberic acid (186) and gibberellin A5 (188), respectively.75' Radioactive gibberellin A5 (187) was

prepared by hydrogenation of gibberellin A3 derivative 189 with tritium gas followed by hydrolysis. Radioactive gibberellin A3 (190) was derived from 187 by oxidation with

0s04. Radioactive gibberellin A20 (191) was prepared by hydrogenation of gibberellin A5

R' H.0 H ,0H s.2OR i.mORZMs0e.g OH

COaf Co1R.COJl

(184) R=4 (185) R'=H, RZ=cT (189)

(186) R = H (187) R'= T. fkl=H cN,oH

(188) R'= RI =f1 CT = Ho1c` off

r0

T0 H0H

Ho~.11offrOltoffso'OH COINCOIN coI1 0.•

(190)(191) (192)

(126)


derivative 192 with tritium gas followed by removal of epoxide oxygen and hydrolysis.761 The total synthesis of gibberellin A15 (194) and A37 (195) using optically active relay

compound 193 which had been derived from enmein (196) were accomplished through

a route summarized in Chart 9 and the chemical conversion of enmein into gibberellin

A15 and A37 was also achieved through a route summarized in Chart 10.67j

OT11,tIV OMe •0Me00— -^I0--^ -r 0 • ----Meo '. H off Me 0

(193)o%-4>(A)

loMeOMeH Meo

od•,~l~ ®~Meo.. . HOMs~'Meotil/. •HOH OHOMe j~O0 0 Me 0,.L.CHO O

(B)

H4 HH

(S woe --. cs owe _______. meg •/4s, H0H CrCoQMe OH0 COAMe 00e COtlie

II H.1 H

woo—~Ho~: H/0COsHCOj.Me0 C0 t

(194)(195)

Chart 9 o UL4 0 ® ..Q~"offi,. t.Oe HOO ----->(H,;c0pe000O'0'OH

t.OH`""0.OHHoff

(196)(197) (198)

4 0Me Chart 9 (197) —> Meo O. ----> (B) '-------> CrA,s (194) "

and G A3T (195) or-. (A)

Chart 9 $~.oMe /~.OMe(B)

—

(198) ---,-->OV o—'--O rs •.OMs,y~t MeoMOll OH

0mOMe

Me0VW --- H•OH

.-0 0

Chart 10

(127)

E. FUJITA, K. Fuji, Y. NAGAO, and M. NODE

A review on the synthesis of gibberellins was published.")

XII. ATISANE DERIVATIVES

N Is

20 11 i3 q11

2 1 10 N 8 3 4 5 6 7

ti II Is

Atisane

It was found evidence that host-plant resistance to the sunflower moth (Homoeosoma

el ectell u m) is caused by trachyloban-19-oic acid (199) and kaurenoic acid (107).88) Isosideritol isolated from Sideritis angustifolia was identified as the atisenetriol (200) •78)

OH

(I 110111111111.so

OH

eo:H•H

(199)(200)

It was concluded that atisine (201) in non-ionic solvents exists as a mixture of C-20

epimers without interconversion via a zwitterion of any type and in ionic solvent isomer-

izes slowly to isoatisine (204) via the intermediate species 202 and 203 in Chart 11.79j

®...-0Da.,(1-11) DH YgVa

>j D,o(cD30D)(.44.1 D20III1H`--a(`"f` N~_H DP"' N''''DOyo;•

(201)(202)(203) (204)

Chart 11

The 13C NMR analysis of atisine (201) and related alkaloids confirmed the

existence of C-20 epimers. Because atisine and related alkaloids are isolated as the

ternary iminium salts (e. g. 205) which on treatment with base generate the respective

alkaloids, the question of which of the C-20 epimers of each alkaloid occurs in the plant

is unanswered.591 The compound 206 was synthesized by Wiesner and his collaborators

by a method that they wished to utilize in the synthesis of delphinium alkaloids.

Further chemical studies, however, ascertained that the compound had failed to rear-

range as predicted and 207 was then proposed. The actual structure found by the

X-ray analysis was 208.8o1

(128)


HO.

cle 'OMeOMe: :00,roffoNoMe 1.off,~ow.~' I11

(205) (206) (207) (208)

XIIL ACOEDERIVATIVES

N 1 u'316

Ai

4DEN 17 it

Aconane

The structure of delphidine (209), a C19-diterpenoid alkaloid isolated from Delphi-nium staphisagria, was elucidated.B1) Three diterpene alkaloids from the roots of Aconium

falconeri were identified as veratroylpseudaconine (210), pseudaconitine (211), and indaconitine (212) by a successful application of 1H and 13C NMR spectroscopy.") Condelphine (213) isolated from Delphinium denudatum was investigated by an X-ray analysis of its hydroiodide derivative.83) The crystal and molecular structure and ab-solute configuration of the 14a-benzoate hydrochloride derivative of chasmanine (214), a diterpene alkaloid of Aconitum chasmanthum, was reported.84)

off

HO•::.f0 €Mto..:;~OMe(210)R'=H,R'•=Veratroyl 1Io.I,s Et"..•Et-0....(211)R=Ac,RaVerafroyl OAc Ho'are

No Mt Me0 OMe(212) RI=Ac, Rs=beKsoyI

(209)

Ho0...pAcrOMeMeo.bH'~M` Et--11

Et•off•. .OH

Imo Me0OMe (213)(214)

The structures of falaconitine (215) and mithaconitine (216), two novel diterpene alkaloids isolated from Aconitum falconeri, were established. These are the first natu-rally occurring aconane alkaloids which contain a C (8) , C (15) double bond.85)

Some reactions using delcosine (lucaconine) (217), anhydrodiacetyldelcosine (anhy-

(129)


drodiacetyllucaconine) (218), and their related compounds, were reported.86>

OH

OMe....... OMe_ OMe i.a-OR°N IOMe Ac0... Et••,0f- Et',.OHEt i'OAa

MeOOMeMee Oy^01Me0 MOMQO

(215) R = veratrvl (217) (218)

(216) R benzoyl

8-Acetyl-14-benzoylneoline (219) was derived from delphisine (220) via some steps

by Pelletier et al. They pointed out that the suggested structure of 8-acetyl-14-ben-

zoylneoline based on the reported data for neopelline is in error and the existence of

neopelline in nature is doubtful.87)

Stereoselective syntheses of the methoxy ketal 221, which had been previously trans-

formed to the chasmanine model compound 222, were described.88>

FI

HO. OMe ArH`CO~OMe Et-...~RHQ84° ,;.•H: oikOH MOOMe~'

(219) R = benzoyl(222) (221)

(220) R = Ac

XIV. TAXANE DERIVATIVES

Is19 H to 4

11 II ; 14 8 1) Is .. ,q. 1 11 3

H 2 H so Taxane

No papers were published in this period.

XV. THE OTHERS

A new cembrenoid diterpene was obtained from a Sarcophyton species of soft coral

and its structure 223 was clarified by the spectroscopic evidence and the X-ray analy-sis.ss)

Absolute configuration of isocembrol (224) and its stereospecific synthesis from cembrene were described.90)

Asperdiol (225) was isolated from gorgonians, Eunicea asperula and E. tourneforti,

(130)


as an anticancer agent against p-388 lymphocytic leukemia in vivo. The structure and

absolute configuration were determined by the X-ray crystallography.91>

Ho off ~H

offo Ho ,.b

(223)(224)(225)

The structure 226 of lobolide, a new epoxy cembranolide from marine origin

(Lobopyytum species), was deduced on the basis of the several spectral data.92> The structure and relative stereochemistry of dihydroxyserrulatic acid (227) were

determined by the chemical degradation reaction and the X-ray analysis.93>

on 0 o/~ 0co1H

cH1oAcH — cuzoH

(226)(227)

Sacculatal (228) and isosacculatal (229), two new exceptional diterpene dialdehydes, were isolated from the liverwort, Trichocoleopsis sacculata.94>

Three novel perhydroazulene type diterpenes, dictyol C, D, and E (230-232), were isolated from both the digestive gland of Aplysia depilans and algae of the family

Dictyotaceae.95>

CHOcHOH off cy0c:j:::JNO N.ryOH

(228)(229)(230)

HO HH

HH OHHO

(231)(232)

The antibiotic extracts of the marine alga Dictyota acutiloba were examined and

two new unusual diterpenoids, dictyoxepin (233) and dictyolene (234) were isolated.ss>

(131)


Pachydictyol A epoxide (235) was isolated from D. flabellata and acetoxycrenulatin

(236) from Pachydictyon coriaceum and D. crenulata and their structures were deter-mined on the basis of their spectroscopic data and chemical correlations.971

0

UHo~oAc

014L1/.\/y1-1 HH OH H (c8=)cN=tMez (cH~,cN=cMez H0

(233)(234)(235)(236)

A crystal-structure analysis of 6-acetyldolatriol (237), an antineoplastic active diter-

pene, isolated from an Indian Ocean sea hare (Dolabella sp.) revealed an unusual molecular packing scheme consistent with the space group R3.980

The X-ray analysis of briarein A (238) isolated from the gorgonian Briareum asbes-tinum was published.")

The structure of ptilosarcone, a toxic component of the sea pen Ptilosarcus gurenegi was suggested as shown in the formula 239,100) which was very similar to briarein A.

00 ONOAc0 oN

N ;oAcoAc 0,OfH O

clHo oAc OHOA

o OAc— • bcco7

0

(237)(238)(239)

Stylatulide (240), the major toxic metabolite of Stylatula sp., was isolated. This

structure was determined by X-ray analysis.101'

0Ac H .0

Cl., . -011 11.

oAc 0Ac

(240)

Methanol-preserved latices of Euphorbia poisonii and E. unispina were examined

for irritant principles. Six 12-deoxyphorbol ester derivatives, 241-246, were identified by spectroscopic and chemical data.l°21 A new phorbol triester 247 was obtained from

the latices of Euphorbia frankiana and E. coerulescens.1031 The structure 248 of 4a-

sapinine, a non-irritant diterpene ester isolated from Sapium indicum, was reported. It

is the first example of a diterpene ester alkaloid of the phorbol type.104)

(132)


NHMe oMe 0

R2(241)R'=Ac, R=H,R3= -c-cH-Et 0c 1--b OR3Me. ,Me (242) R'=Ac,R`=H, R3=-'~t=c,HOAc

3:I00H=: ®'•(243) R'=Ac,(t`=H.R3=-e-cHMe:.iii, OHc MetiWH 0/(244) R'=R'= H,R3=-c-cH Et 0/

cH10R1(245) R'=R'=H, R3: _r&=c`HeMon

0

(246) R' = Rz=H, g3= -5-CHMBx(248)

0

(247) IV= -o-MQc:se,R='oo•cHMea,R3=Ac Four new highly irritant diterpenes, 249-252, were isolated from Euphorbia tirucalli,

in addition to some inactive isomers.'O" The CD spectral studies of phorbol and of some

of its derivatives were published.10'"

Toxic compounds were isolated from Euphorbia Millii. These are milliamine A

(253), B (254), and C (255), the structures of which were determined from chemical

and spectral evidence.10"

OR'H .... .

..

. H~R1i O..H

,H••./H ~oH/ 0 H~0q' z

cH10HOH CH:OR

~ZE (249)R= coeH=cHcH=cNcH=cH(cH,1:Me,(253) R`=X. R3=Ac

R1y- pc 1z E(254) R'=H123=X.'=X R (250)' -Ac.R=COCH=6HCH=cHCHcn(CH,LMe (255) RI=X . R'=H

(251) RI= Ac. re= Co(cH=cH)r(CH,htie-cc H a

(252) R'=Ac,R1=Co (of =cH)4(CH.A4MexV'o HHOo PI e1N.6 Regio- and stereo-selective synthesis of thunbergol (256) and its epimer (257) was

achieved to establish the stereostructure of thunbergol which had remained unsolved.10'"

Likewise, in order to determine the stereochemistry of incensole (258) and isoincensole-

oxide, (259), they were stereoselectively synthesized from rac-mukulol (260) and its

epimer (262)."'

,,, :oHHo.,' b.4

A H0:Ho,/0~4

r

(256) (257)(258)R (259)(260) R = (3-OH

(261) R = d- 01f

(133)

E. FuJiTA, K. Fug, Y. NAGAO, and M. NODE

Intermolecular acylation of geranylfarnesic acid chloride (262) was successfully

performed to afford albocerol skeleton 263, which was converted to 264. The com-pound 264, an analogue of the termite trail pheromone, neocembrene (265), showed also the pheromone activity.110

Oxidation of cembrene with Cr03 in aqueous acetone gave two epimeric cembratri-enediols 266 and 267."

off

cl~ c

00 ~_ R (264) R-- CNzcH=cMez(266)R=e-Mc

(262)(263)(3-OH (265) R= H(267) R= 0(..o I.

fl- Me

Cembrene epoxides, 268-271, were obtained by epoxidation of cembrene with per- acetic acid and perbenzoicacid."

H0 H

t/N/-4';;;;1 (268)(269)(270) (271)

All trans-a-retinyl-11-3H acetate (272) was prepared in 10 steps from ethyl a-

iomylidene acetate and had a specific activity of 2.65 Ci/mmol and radiochemical

purity >99%.113) A stereochemically defined synthesis of compound 273 was described."41

H 3H 0

C!laOAc,~ Meo

(272)(273)

The X-ray analysis of ent-9 (8--->15aH) ab eo- 17-norkaur- 8 (14) -en-16-one (149) provid-ed a confirmation115' of the structure and stereochemistry as expected previously.") A review article "Stereo- and ragiochemistry of the Claisen rearrangement applications to natural products synthesis" was published. Several reactions which appeared in this review must be very usuful for diterpene synthesis."s'

In a review on the tumor inhibitors having potential for interaction with mercapto enzymes and/or coenzymes, many diterpenes possessing unique chemical structures were

(134)


described. The creative idea and discussions in this paper may serve in the develop-ment of the new SH alkylating antitumor agents.117j

A Japanese review in relation to the insect-growth regulators from drug plants was

reported, in which cinnzeylanine (274), cinnzeylanol (275), and dimethyl sciadinonate

(276) were cited.18>

RMcO ,co off

H 0 1110111P Hv•. HOOHMeqcco,H

(274) R = A c(276)(277)

(275) R =

A review described on antheridiogen-An (277) was reported in Japanese.119> A

review "The structure and synthesis of C,, diterpenoid alkaloids" was published."" The "C, NMR of 20 tricyclic aromatic diterpenoids were reported .12) Many diterpenes were

isolated from the leaves and stem bark of Cupressus torulosa.122> Several other papers i. e. "Hyptol from Hyptis fructicosa" ,"> "Doronicoside D from Doronicum macrophyllum",121> and "O-Acetyldelektin, a new alkaloid from Delphinium dictyocarpum","5> were also

published.

REFERENCES

(1) For 1976 see E. Fujita, K. Fuji, Y. Nagao, M. Node, and M. Ochiai, Bull. Inst. Chem. Res., Kyoto Univ., 55, 494 (1977).

(2) S. C. Welch, C. P. Hagan, J. H. Kim, and P. S. Chu, J. Org. Chem., 42, 2879 (1977). (3) S. W. Pelletier and Y. Ohtsuka, Tetrahedron, 33, 1021. (1977). (4) W. S. Hancock, L. N. Mander, and R. A. Massy-Westrpp, Aust. J. Chem., 30, 1093 (1977). (5) Y. Ichinoe, Kagaku no Ryoiki, 31, 248 (1977). (6) S. Okuda, S. Sanai, and the late A. Tahara, Nippon Nogeikagaku Kaishi, 51, 227 (1977). (7) J. S. Prasad and H. G. Krishnamurity, Phytochemistry, 16, 801 (1977). (8) S. Braun and H. Breitenbach, Tetrahedron, 33, 145 (1977). (9) F. Bohlmann and M. Grenz, Chem. Ber., 110, 1321 (1977). (10) A. G. Gonzalez, J. M. Arteaga, J. L. Breton, and B. M. Fraga, Phytochemistry, 16, 107 (1977). (11) S. V. Bhat, B. S. Bajwa, H. Dornauer, N. J. de Souza, and H. -W. Fehlhaber, Tetrahedron

Lett., 1669 (1977). (12) S. Yamamura and Y. Terada, Tetrahedron Lett., 2171 (1977). (13) F. Bohlmann, C. Zdero, and M. Grenz, Chem. Ber., 110, 1034 (1977). (14) . G.. Savona, .F. Piozzi, J. R. Hanson, and M. Siverns, J. C. S. Perkin Trans. I, 497 (1977). (15) Idem., ibid., 322 (1977). (16) P. Sundaraman and W. Herz, J. Org. Chem., 42, 806 (1977). (17) :Idem., ibid., 42, 813 (1977). (18) - I. Wahlberg, K. Karlsson, T. Nishida, K. Cheng, C. R. Enzell, J.-E. Berg, and A. -M. Pilotti,

Acta Chem. Scand., B31, 453 (1977). (19) I. Kitagawa, M. Yoshihara, and T. Kamigauchi, Tetrahedron Lett., 1221 (1977). (20) G. B. Oganesyan and V. A. Mnatsakanyan, Khim. Prir. Soedin., 215 (1977). (Chem. Abstr., 87,

184719s [1977].) (21) B. Dockerill and J. R. Hanson, J. C. S. Perkin Trans. I, 324 (1977).

(135)

E. FUJITA, K. FUJI, Y. NAGAO, and M. NODE

(22) N. Cagnoli-Bellavita, P. Ceccherelli, M. Ribaldi, J. Polonsky, Z. Baskevitch-Varon, and J. Varenne, ibid., 351 (1977).

(23) F. Orsini, F. Pellizoni, A. T. McPhail, K. D. Onan, and E. Wenkert, Tetrahedron Lett., 1085 (1977).

(24) T. Kato, M. Tsunakawa, N. Sasaki, H. Aizawa, K. Fujita, (the late) Y. Kitahara, and N. Takahashi, Phytochemistry, 16, 45 (1977).

(25) D. Cartwright, P. Langcake, R. J. Pryce, D. P. Lewarthy, and J. P. Pide, Nature, 267, 511 (1977).

(26) T. Kato, H. Aizawa, M. Tsunakawa, N. Sasaki, (the late) Y. Kitahara, and N. Takahashi, J. C. S. Perkin Trans. I, 250 (1977).

(27) H. Enomoto, Y. Yoshikuni, Y. Yasutomi, K. Ohata, K. Sempuku, K. Kitaguchi, Y. Fujita, and T. Mori, Chem. Pharm. Bull. (Tokyo), 25, 507 (1977).

(28) P. Ruedi and C. H. Eugster, Hely. Chim. Acta, 60, 1233 (1977). (29) S. Arihara, P. Ruedi, and C. H. Eugster, ibid., 60, 1443 (1977). (30) R. Zelnik, D. Lavie, E. C. Levy, A. H. -J. Wang. and I. C. Paul, Tetrahedron, 33, 1457 (1977). (31) R. Zelnik, J. A. McMillan, I. C. Paul, D. Lavie, V. G. Toscano, and R. Dasilva, J. Org. Chem.,

42, 923 (1977).

(32) Y. Inoue and M. Ishigami, Yukagaku, 26, 176 (1977). (Chem. Abstr., 87, 39689c [1977].) (33) T. Matsumoto, Y. Ohsuga, S. Harada, and K. Fukui, Bull. Chem. Soc. Japan, 50, 266 (1977). (34) T. Matsumoto, S. Usui, and T. Morimoto, ibid., 50, 1575 (1977). (35) H. Akita, K. Mori, and A. Tahara, Chem. Pharm. Bull. (Tokyo), 25, 974 (1977). (36) M. I. Goryaev, F. S. Sharipova, L. K. Tikhonova, and F. S. Nigmatullina, Izv. Akad. Nauk. kaz.

SS R, Ser. Khim., 27, 68 (1977). (Chem. Abstr., 87, 102466v [1977].)

(37) W. Herz, R. C. Ligon, J. A. Turner, and J. F. Blount, J. Org. Chem., 42, 1885 (1977). (38) J. A. Turner and W. Herz, ibid., 42, 2006 (1977). (39) W. Herz, V. S. Iyer, M. G. Nair, and J. Saltiel, J. Am. Chem. Soc., 99, 2704 (1977). (40) D. Svikle, A. Kalnins, A. Prikule, and R. Rasina, Khim. Drev,. 114 (1977). (Chem. Abstr., 88,

23184u [19781.) (41) J. W. Huffman and P. G. Harris, Synth. Comm., 7, 137 (1977). (42) T. Matsumoto and T. Ohmura, Chem. Lett., 335 (1977). (43) A. Matsuo, J. Kodama, M. Nakayama, and S. Hayashi, Phytochemistry, 16, 489 (1977). (44) I. Beneg, V. Benegova, and V. Herout, Collection Czechoslov. Chem. Comm., 42, 1229 (1977). (45) M. Przybylska and F. R. Ahmed, Acta Cryst., B33, 366 (1977). (46) F. Bohlmann and C. Zdero, Phytochemistry, 16, 492 (1977). (47) F. Bohlmann and N. Le Van, ibid., 16, 579 (1977). (48) F. Bohlmann and C. Zdero, ibid., 16, 786 (1977). (49) A. Matsuo, S. Uto, M. Nakayama, and S. Hayashi, Chem. Lett., 327 (1977). (50) I. Kubo, K. Nakanishi, T. Kamikawa, T. Isobe, and T. Kubota, Chem. Lett., 99 (1977). (51) H. Fukui, K. Koshimizu, S. Usuda, and Y. Yamazaki, Agr. Biol. Chem., 41, 175 (1977). (52) H. Fukui, R. Nemori, K. Koshimizu, and Y. Yamazaki, ibid., 41, 181 (1977). (53) H. Richter, H. Obermann, and G. Spiteller, Chem. Ber., 110, 1963 (1977). (54) I. Sakamoto, K. Yamazaki, and O. Tanaka, Chem. Pharm. Bull. (Tokyo), 25, 844 (1977) (55) H. Hikino, M. Ogura, S. Fushiya, C. Konno, and T. Takemoto, ibid., 25, 523 (1977). (56) R. Kasai, M. Suzuno, J. Asakawa, and O. Tanaka, Tetrahedron Lett., 175 (1977). (57) R. A. Cruz, R. C. Castillo, F. J. Carcia, and R. I. Reed, Org. Mass. Spectrom., 12, 21 (1977).

(Chem. Abstr., 87, 136010g [1977].) (58) A. C. Waiss, Jr., B. G. Chan, C. A. Elliger, and V. H. Garrett, Naturwissenschaften, 64, 341

(1977). (59) S. W. Pelletier and N. V. Mody, J. Am. Chem. Soc., 99, 284 (1977). (60) R. Neidler and V. Stumpf, Arzneim-Forsch., 27, 999 (1977). (Chem. Abstr., 87, 201801g 11977].) (61) K. Nabeta, K. Ito, and H. Sugisawa, Nippon Nogeikagaku Kaishi, 51, 179 (1977). (62) H. Sugisawa, T. Kasai, and H. Suzuki, ibid., 51, 175 (1977). (63) R. C. Cambie, W. I. Noall, G. J. Potter, P. S. Rutledge, and P. D. Woodgate, J. C. S. Perkin

Trans. I, 226 (1977). (64) E. Fujita and M. Ochiai, ibid., 1182 (1977). (65) F. E. Ziegler and J. A. Kloek, Tetrahedron, 33, 373 (1977).

(136)


(66) T. Kato, T. Suzuki, N. Ototani, H. Maeda, K. Yamada, and (the late) Y. Kitahara, J. C. S. Perkin Trans I, 206 (1977).

(67) E. Fujita, M. Node, and H. Hori, ibid., 611 (1977). (68) A. A. Chalmers, C. P. Gorst-Allman, and L. P. L. Piacenza, Tetrahedron Lett., 1665 (1977).

(69) G. C. Martin, F. G. Dennis, Jr., P. Gaskin, and J. MacMillan, Phytochemistry, 16, 605 (1977). (70) S. Okuda, S. Sanai, and (the late) A. Tahara, Nippon Nogeikagaku Kaishi, 51, 223 (1977).

(71) D. Voigt, G. Adam, J. Schmidt, and K. Schreiber, Org. Mass Spectrom., 12, 169 (1977). (72) R. E. Banks and B. E. Cross, J. C. S. Perkin Trans. I, 512 (1977).

(73) G. Adam, M. Lishewski, F.-J. Sych, and A. Ulrich, Tetrahedron, 31, 95 (1977). (74) G. Schneider, G. Sembdner, and K. Schreiber, ibid., 33, 1391 (1977).

(75) G. Schneider, O. Miersch, and H.-W. Liebisch, Tetrahedron Lett., 405 (1977). (76) N. Murofushi, R. C. Durley, and R. P. Pharis, Agr. Biol. Chem., 41, 1075 (1977).

(77) E. Fujita and M. Node, Heterocycles, 7, 709 (1977). (78) M. I. Garrascal, B. Rodriguez, and S. Valverde, An. Quim., 73, 442 (1977). (Chem. Abstr., 87,

152417a [1977].) (79) S. W. Pelletier and N. V. Mody, Tetrahedron Lett., 1477 (1977).

(80) A. D. Hardy and F. R. Ahmed, Acta Cryst., B33, 1283 (1977). (81) S. W. Pelletier, J. K. Thakkar, N. V. Mody, Z. Djarmati, and J. Bhattacharyya, Phytochemistry,

16, 404 (1977). (82) S. W. Pelletier, N. V. Mody, and H. S. Puri, ibid., 16, 623 (1977).

(83) S. W. Pelletier, W. H. DeCamp, D. L. Herald, Jr, S. W. Page, and M. G. Newton, Acta Cryst., B33, 716 (1977).

(84) W. H. DeCamp and S. W. Pelletier, ibid., B33, 722 (1977). (85) S. W. Pelletier, N. V. Mody, and H. S. Puri, J. C. S. Chem. Comm., 12 (1977).

(86) T. Amiya, Y. Kanaiwa, N. Nakano, and T. Shima, Bull. Chem. Soc., Japan, 51, 248 (1978). (87) S. W. Pelletier, J. Bhattacharyya, and N. V. Mody, Heterocycles, 6, 463 (1977).

(88) K. Wiesner, I. H. Sanchez, K. S. Atwal, and S. F. Lee, Can. J. Chem., 55, 1091 (1977). (89) J. C. Coll, G. B. Hawes, N. Liyanage, W. OberhansIi, and R. J. Wells, Australian J. Chem., 30,

1305 (1977). (90) V. A. Raldugin and V. A. Pentegova, Khim. Prirodn. Soedin., 577 (1977). (Chem. Abstr., 87,

201810j [1977.) (91) A. J. Weinheimer, J. A. Matson, D. van der Helm, and M. Poling, Tetrahedron Lett., 1295

(1977). (92) Y. Kashman and A. Groweiss, ibid., 1159 (1977).

(93) K. D. Croft, E. L. Ghisalberti, P. R. Jefferies, C. L. Raston, A. H. White, and S. R. Hall, Tetrahedron, 33, 1475 (1977).

(94) Y. Asakawa, T. Takemoto, M. Toyota, and T. Aratani, Tetrahedron Lett., 1407 (1977). (95) B. Danise, L. Minale, R. Riccio, V. Amico, G. Oriente, M. Piattelli, C. Tringali, E. Fattorusso,

S. Maguo, and L. Mayol, Experientia, 15, 413 (1977). (96) H. H. Sun, S. M. Waraszkiewicz, K. L. Erickson, J. Finer, and J. Clardy, J. Am. Chem. Soc.,

99, 3516 (1977). (97) F. J. McEnroe, K. J. Robertson, and W. Fenical, NATO Conf. Ser., (Ser.) 4 (Mar. Nat. Prod.

Chem.), 179 (1977). (Chem. Abstr., 88, 37993u [1978].) (98) R. B. VonDreele, Acta Cryst., B33, 1047 (1977).

(99) J. E. Burks, D. van der Helm, C. Y. Chang, and L. S. Ciereszko, ibid., B33, 704 (1977). (100) S. J. Wratten, W. Fenical, D. Faulkner, and J. C. Wekell, Tetrahedron Lett., 1559 (1977). (101) S. J. Wratten, D. J. Faulkner, K. Hirotsu, and J. Clardy, J. Am. Chem. Soc., 99, 2824 (1977). (102) R. J. Schmidt and F. J. Evans, Lloydia, 40, 225 (1977). (103) F. J. Evans, Phytochemistry, 16, 395 (1977). (104) G. A. Miana, R. Schmidt, E. Hecker, M. Shamma, J. L. Moniot, and M. Kiamuddin, Z.

Naturforsch., 32B, 727 (1977). (105) G. Fiirstenberger and E. Hecker, Tetrahedron Lett., 925 (1977). (106) G. Snatzke, L. Hruban, F. Snatzke, R. Schmidt, and E. Hecker, Isr. J. Chem. 15, 46 (1977).

(Chem. Abstr., 88, 37991s [1978].) (107) D. Uemura and Y. Hirata, Bull. Chem. Soc. Japan, 50, 2005 (1977). (108) T. Kato, M. Suzuki, M. Takahashi, and Y. Kitahara, Chemistry Lett., 465 (1977).

(137)

E. FUJITA, K. Fug, Y. NAGAO, and M. NODE

(109) T. Kato, C. C. Yen, T. Uyehara, and (the late) Y. Kitahara, ibid., 565 (1977). (110) T. Kato, M. Suzuki, Y. Nakazima, K. Shimizu, and (the late) Y. Kitahara, ibid., 705 (1977). (111) V. A. Raldugin, A. I. Rezvukhin, L. Ya. Korotkikh, and V. A. Pentegova, Khim. Prirodn.

Soedin., 54 (1977). (Chem. Abstr., 87, 117968j 119771.) (112) - V. A. Raldugin, L. Ya. Korotkikh, A. I. Rezvukhin, and V. A. Pentegova, ibid., 525 (1977).

(Chem. Abstr., 88, 37992t [1978].) (113) R. L. Hale, W. Burger, C. W. Perry A. A. Liebman, J. Labelled Compd. Radiopharm., 13, 123

(1977). (Chem. Abstr., 87, 23541n [1977].) (114) U. R. Ghatak and J. K. Ray, J. C. S. Perkin Trans I, 518 (1977). (115) T. Taga, T. Higashi, H. Iizuka, K. Osaki, M. Ochiai, and E. Fujita, Acta. Cryst., B33, 298 (1977). (116) F. E. Ziegler, Accounts of Chem. Res., 10, 227 (1977). (117) E. Fujita and Y. Nagao, Bioorg. Chem., 6, 287 (1977). (118) A. Isogai, Nippon Nogeikagaku Kaishi, 51, R 47. (1977). (119) K. Takeno and M. Furuya, Shokubutsu no Kagaku. Chosetsu (Chem. Regulation of Plants), 12, 16

(1977). (120) S. W. Pelletier and S. W. Page, Int. Rev. Sci.: Org. Chem., Ser. Two, 9, 53 (1976). (121) T. Nishida, I. Wahlberg, and C. R. Enzell, Org. Magn. Reson., 9, 203 (1977). (Chem. Abstr., 88,

7096m [1977].) (122) J. S. Prasad and H. G. Krishnamurty, Indian J. Chem., 15B, 397 (1977). (123) F. D. Monache, F. Marletti, G. Marinibettolo, J. F. D. Mello, and L. L. Dalbuquerque, Gazz.

Chim. Ital., 107, 319 (1977). (124) Sh. A. Alieva, Z. M. Putieva, E. S. Kondratenko, and N. K. Abubakirov, Khim. Prirodn. Soedin.,

658 (1977). (125) B. T. Salimov, M. S. Yunusov, and S. Yu. Yunusov, ibid., 716 (1977).

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