Embed Size (px)
Citation preview
Robert V. Stevens
1
Jun ShiBaran Group Meeting19/11/2008
Biographical Information:
-Born on March 24, 1941 in Mason City, Iowa-Received B.S. degree in 1963 in Iowa State University-Ph. D at Indiana University with Professor Ernest Wenkert (1963-1966)-Appointed to the faculty of Rice University (1966-1977)-Professor of Chemistry in UCLA (1977-1984)-Deceased on March 9, 1984
Robert V. Stevens
"Professor Stevens was a special kind of teacher. He would shuffle into an undergraduateclass, clear his throat, and say, "Unhuh." The metamorphosis came when he picked up the chalk. No one who saw Professor Stevens work with chalk and the elegant structures he drew will forget the simple beauty of his lectures. He was a transformed man with chalk in his hands. His dry wit and diffident charm cane through with clarity, and his sense of styleand art pervaded the room" -Professor Orville L. Chapman of UCLA
Summary of research interests throughout Professor Stevens's career:-Total synthesis of natural products -alkaloids -steroids -vitamins-Development of chemical methods in synthesis -rearrangement of cycloproplyimines -stereocontrolled nucleophilic attack on immonium ions -nitrone addtions
Alkaloids synthsis by rearrangement of cyclopropyl imines
R3R2
N R1
H+, 100°C NR1
R2
R3
CNN
Li
NH
N N
Myosmine
NH
HCl, cat.
100°C20mins70%
TL, 1967, 5158TL, 1968
SPh
N
1. NH4Cl
2. HCl, MeOH N
PhS
SPh
N
OO 1. NH4Cl, reflux, xylene, 88%
2. HCl, MeOH, 90% N
PhSOMe
OMe
EtO
OEt
CHO
TL, 1976, 3799
Studies on total Syntheses of Alkaloids
100-160°C55%-90%
Synthesis of pyrrolizidine and indolizidine necleus
N
indolizidine δ-coniceine
pyrrolizidine
N
CH2OH
(±)-isoretronecanol
Robert V. Stevens
2
Jun ShiBaran Group Meeting19/11/2008
N
O
Me
2. MeNH2
NH4I, ! MVK MeO
MeO
dl-Mesembrine
JACS, 90, 1968, 5580
CO2Me
O
N
OMe
Me
O
N
OMe
OMe
Me
N
1.CH(OMe)3
2. DIBAL-H3. NH2OH•HCl
Sceletium A-4 JOC, 1975, 3495
EtO2C
NEt
O
O
1. NH4Cl
2. HCl
N
EtCO2Et
O
1. NaOMe2. LAH
3. H2/Pd
, H+
N
H Et
O
N
H Et
NAc
OMe
(±)-AspidospermineCC, 1971, 857
N
OMe
O
MeI
Me MeN
OH
O
Me Me
HBr
(±)-Joubertiamine
JOC, 1972, 2138
BnN
O
O
O
1. iPrOH, Pd/C
2. H2/Pd3. CH2O
N
OH
O
O
dl-Elwesine
JOC, 1972, 977
N
OMe
OMe
Me CO2Me
O
Applications to complex nature product
OMe
OMe
CN
OMe
OMe
C
NMe
1. DIBAL
N
Me
OMe
OMe
A formal synthesis of (±)-Aspidospermine
Acid catalysed rearrangement of cyclobutylimines synthesis of tetrahydropyridines
R1
R2
N
R3
170°C
NH4Br or NH4Cl N
R1
R2
R3
30%-66%JCS, CC, 1975, 682
Robert V. Stevens
3
Jun ShiBaran Group Meeting19/11/2008
Total synthesis of precoccinelline and coccinelline with Robinson-Schopf reaction as the key step
NH2
CH(OMe)2
CH(OMe)2
MeO2C CO2Me
O N
OE
E
1. DMF, reflux
2. Ph3P=CH2
NH
CH2
Pd/H2
NH
CH3
Coccinelline
NH
CH3
Precoccinelline
mCPBAO
JACS, 1979, 7032
O O NH O O
N
Me
O
N
O
Me
TsOH
OAc
HCl
Hg(OAc)2
HOAc
N
O
Me
1. TsOH
2. TsNHNH2
then tBuLiNMe
N
Me
H(±)-porantherine
JACS, 1987, 4940
Me
Me
H2CNH
CN
1. Hg(NO3)2
2. NaBH4
NH
NH
HN
Me
Me
H2C
HN
Me
Me
Me
HCl
(+)-Makomakine
(+)-Aristoteline
Me
Me
H3CNH
CN
1. Hg(NO3)2
2. NaBH4 NH
HN
Me
Me
H3C
(+)-Hobartine
JCS, CC, 1983, 384
Me
O1. Hg(NO3)2, MeCN
2. 1 eq NaBH4
Me
H3COCHN
O
Use of nitriles as terminatiors of carbacation-olefin cyclization
JOC, 1985, 632
Stereorational total synthesis of (±)-porantherine
Expeditious stereospecific total syntheses of (+)-Makomakine, (+)-Aristotelineand (+)-Hobartine
pH=1
N
Robert V. Stevens
4
Jun ShiBaran Group Meeting19/11/2008
N
O
1. AcNO2
2. H2/PtO2
3. POCl3N
N
NH2
N
N
N
Me
Me
KHFe(CO)4
CH2OCO
Vasicoline
N
N
N
Me
Me
O
air
Vasicolinone
MeO2C NC
CO2Me
CuO
HN
MeO2C
CO2Me
N
N
CO2Me
O
O
O
HN
O
O
JOC, 1988, 1873
JCS, CC, 1975, 742
N
O
O
OMe
OMe
OO
OMe
OMe
O Me
Karachine
OTMS Me
JCS, CC,1983, 1425
Synthesis of pyrrolobenzodiazepine nucleus of anthramycin
py.
Expeditious total synthesis fo karachine
Total syntheses of vasicoline and vasicolinone
Studies on benzocyclobutenones and total synthesis of (±)-taxodione
OMe
MeO
Me
Me
Br
NaNH2
MeO OMe
OMe
MeO
Me
Me
O
1.
Me Me
Me
Cl
2. KOtBu tBuOH
Me Me
Me
O
OMe
MeO
Me
Me
Me Me
Me
O
O
HO
Me
Me
HCO2HH3PO4
reflux
Me Me
Me
O
OMe
MeO
Me
Me
1. BBr3
2. SiO2
(±)-taxodione
JOC, 1982, 2393JOC, 1982, 2396
Li/EtOH
Cl
Berberine
DMSO, 100°C
66%
Robert V. Stevens
5
Jun ShiBaran Group Meeting19/11/2008
Studies on Spiro-Activated Cyclopropanes
1. synthesis of cyclopropane
O O
N2
OO
Me MeO
O
O
O
Me
Me
O
OOMe
Me
O
2. Homoconjugated addtion of Grignard
TBSO
O O
N2
OO
Me Me
TBSO
O
O
O
O
Me
Me
TBSO
O
O
O
SMe
Me
Me
Me
O
O
O
SMe
BrMg
OO
Me
OH
HO
(±)-Brefeldin A
JCS, CC, 1978, 754JACS, 1978, 6479JOC, 1980, 2780
hv, 253.7nm
byproduct
hv
Studies on Quassinoids
CH2OH
OH
OCH3
salcomine
O2
CH2OH
O
OCH3
O
CO2Me
O
O
CO2Me
OCH3
CH2OH
OAc
O
CO2Me
OCH3
CH2OH
O
O
OCH3
SePhO
OAc
O
CO2Me
OCH3
SePhO
O
PhSeCl
1. NaOH2. TsOH
O
OCH3
OHO
O
Me
O
HO
MeOH
Me
MeMe
Me
O
Bruceantin
JOC, 1985, 4056JOC, 1986, 4347
A B C
D E
B C
D E
Robert V. Stevens
6
Jun ShiBaran Group Meeting19/11/2008
Total synthesis of steroids and vitamine D3 using camphorae as chiral intermediate
OMeI
MeNHOH
MeMeMeO2C
1. NaCH(CO2CH3)2
2. NH2OH MeO2C
CN
Me CH2
TsCl, Py
TFA
CN
Me CH3
MeO2C
Me CH3
CN
O
1.tBuOK2. MVK, NaOEt
OMe
O
OHO
OH
Cortisone
1. SeO22. NaBH43. NBS
MeO2C
MeCN
Br
O
SO2Tol
Me CN
1. NaSO2Tol
2. NaOMe
Me
Me
Me
Me
HOVitamine D3
JACS, 1977, 6105JACS, 1983, 7713T, 1985, 93
Studies on Sodium Hypochlorite "swimming pool chlorine"
1. selective oxidation of secondary alcohol in the presence of primary alcohol
2. conversion of aldehyde to ester
CHONaOCl, TFAMeOH
CO2MeCHO
NaOCl, TFAMeOH
O4 CO2Me
O4
JOC, 1980, 2030, TL, 1982, 4647
Robert V. Stevens
7
Jun ShiBaran Group Meeting19/11/2008
General Method for the nitrile oxide
C N OR
N
R H
OH
N
R Br
OH
N
R H
OH
N
R Cl
OH
Pb(OAc)4
NBSNCS
RCH2NO2
PhNCOEt3N
Isoxazole synthesis and nucleophilic substitutions of 5-choloroisoxazoles
NO
R
Cl
Cl
NO
Cl
R Nu NO
Nu
R
Et3N Et3N
Robert V. Stevens
8
Jun ShiBaran Group Meeting19/11/2008
N
N N
N
CONH2
CH3 CH3CONH2
CONH2
CH3
CH3
CONH2
CH3CH3
H2NOCH
H3C
H3C
H2NOC
Co
CN
N
N N
N
CONH2
CH3 CH3CONH2
CONH2
CH3
CH3
CONH2
CH3CH3
H2NOCH
H3C
H3C
H2NOC
Co
CN
CN
HOOC
NH
O
O
PO
O
OHOH2C
HN
HO N CH3
CH3
Me
Vitamin B12 Cobyric Acid
N
NH N
N
Me
Corrin
Studies on Vitamine B12 and Corrins
Synthetic Strategy
N
O
R
H
R
HN
HO
R
H
R
OH
R
HN
H
HN
N
COX
CO2MeN N
N
O
H3C
H3C
H3CCH3
OCH3
CH3
H3C CH3
O
NCOX
COCH3N
N
A B
CD
H3C
H3C
O
H3C CH3
CH3
CH3
O
O
CH3
H3C
A
B C
D
Total synthesis of Ni Octamethylcorphin
CO2Me
NO2 N
OPhNCOEt3N
CO2Me
O
O
O
O
1. HCl2. NH2OH•HCl
N
O
CO2Me
NOH
A 1. NBS, Et3N, A2. HCl,3. NH2OH•HCl
N
O
CO2Me
ON
N
OH1. NBS
O
N
O
CO2Me
ON
N
O
O
A B C D
89%96%
90%
85%
Robert V. Stevens
9
Jun ShiBaran Group Meeting19/11/2008
N
O
CO2Me
ON
N
O
O
NH2
O
CO2Me
ONH2
H2N
O
ORaney NiH2
Et3N
NH
N O
O
N
O
1. NaOMe
2. Ni(ClO4)2N
N O
O
N
O
Ni
ClO4
1. NH4OAc
2. tBuOK
N
N N
O
N
Ni
ClO4
Studies towards vitamin B12
N
OH
CO2Me
O
O
MeO2C
CONMe2
CO2Me
N
HO
N
CO2Me
O
O
MeO2C
CONMe2
CO2Me
N
HO
O
NCS, Et3N
CO2Me
HON
NC
MeO2C
NO2
NC
MeO2C
NO2
CO2Me
NO
tBuOClEt3N
N
CO2Me
O
O
MeO2C
CONMe2
CO2MeO
NC
MeO2C
O2N
CO2Me
NO
N
O
Cobyric acidVitamin B12
+
90%
93%
JACS, 1971, 6629JACS, 1971, 6637JACS, 1975, 5940 JACS, 1976, 6313
JACS, 1976, 6317JACS, 1983, 7719JACS, 1986, 1039
tBuOClEt3N
![Spiropyrans Containing the Reactive Substituents in the 2H ...B. S. Lukyanov et al. 3 O O O N OHC CH3 OH III Scheme 3 N O CHO CH3 CH3 H3C OH IV Scheme 4 [13]. Also, one can note that](https://img.pdfslide.us/doc/110x75/61112a490c3dfb376e39b282/spiropyrans-containing-the-reactive-substituents-in-the-2h-b-s-lukyanov-et.jpg)
![Effect of Diallyl Sulfide on Rat Liver Microsomal ... · patic oxidation of azomethane (CH3N=NCH3) to azoxy-methane [CH3N=N(O)CH3] to methylazoxymethanol [HOCH2N=N(O)CH3] (11). Since](https://img.pdfslide.us/doc/110x75/606022148482a141a2614263/effect-of-diallyl-sulfide-on-rat-liver-microsomal-patic-oxidation-of-azomethane.jpg)
