Mike DeMartino Baran Group Meeting William Fenical and Satoshi Omura Biography: -Bachelors degree from Yamanashi University -M.S. and Ph. D. from the Science University of Tokyo (1958) -Ph. D. in Pharmacy from University of Tokyo -Currently a professor and the president of the Kitasato Institute of Japan -Research focuses on the isolation and discovery of microorganisms as well as biologically interesting substances which they produce A n t i b a c t e r i a l: A-73A, aurantinins, factumycin, kinamycins, KM-8, LA-1, leucomycins, takaokamycin B a c t e r i a l c e l l w a l l s y n t h e s i s i n h i b i t or: AM-5289, asukamycin, azureomycin, nanaomycins, setomimycin, vineomycins A n t i f o l a t e: AM-8402, diazaquinomycin A n t i m y c o p l a s m a l: 2'-amino-2'-deoxyadenosine, cervinomycins, frenolicin B, OM-173 A n t i a n a e r o b i c: clostomicin, luminamycin, lustromycin, thiotetromycin A n t i v i r a l: virantmycin, virustomycin A n t i f u n g a l: AF-8 (albolleutin), cerulenin irumamycin, O-2867, prumycin A n t i p a r a s i t i c: avermectins, hitachimycin (stubomycin), setamycin A n t i c a n c e r: OS-3256B, sporamycin H e r b i c i d a l: herbimycins, karabemycin P e n i c i l l i n a s e i n h i b i t o r: KA-107 A d e n o s i n e d e a m i n a s e i n h i b i t o r: adechlorin E l a s t a s e i n h i b i t o r: elasnin A n t i p l a t e l e t: OM-3209 A l k a l o i d ( c h e m i c a l s c r e e n i n g ): AM-2504 (prolimycin), 1,3-diphenethylurea, herquline, NA-337 A, neoxaline, pyrindicin, quinoline-2-methanol, staurosporine, TM-64 (narcoactine) H y b r i d b i o s y n t h e s i s: chimeramycins, mederrhodins C h e m i c a l m o d i f i c a t i o n: rokitamycin (3"-O-propionylleucomycin A, 5, 3,3",4"-tri-O-propionylspiramycin I, motilides N e u r i t o g e n e s i s i n d u c e r: lactacystin H M G - C o A s y n t h a s e i n h i b i t o r: 1233A A c y l - C o A s y n t h e t a s e i n h i b i t o r: triacsins A c y l - C o A : c h o l e s t e r o l a c y l - t r a n s f e r a s e ( A C A T ) i n h i b i t o r: pyripyropenes, terpendole, purpactines, glisoprenin G l u t a m i n e s y n t h e t a s e i n h i b i t o r: phosalacine, oxetin P r o t e i n f a r n e s y l t r a n s f e r a s e i n h i b i t o r: pepticinnamin, gliotoxin C e l l u l o s e b i o s y n t h e s i s i n h i b i t o r: phthoramycin, phthoxazolin A n t i c o c c i d i a l: cytosaminomycin, fudecalone, hynapene G p - 1 2 - C D 4 b i n d i n g i n h i b i t o r: chloropeptin, isochromophilones A c e t y l c h o l i n e e s t e r a s e i n h i b i t o r: arisugacin O t h e r s: irumanolides, protylonolide Biological diversity of Professor Omura's isolated chemicals (Taken from Microbiological Reviews, 1986, 50, 259.) P r o f e s s o r S a t o s h i O m u r a Wednesday, May 19, 2004
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Baran Group Meeting William Fenical and Satoshi … Group Meeting William Fenical and Satoshi Omura Mike DeMartino Biography:-Bachelors degree from Yamanashi University-M.S. and Ph.
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Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
Biography:
-Bachelors degree from Yamanashi University
-M.S. and Ph. D. from the Science University of Tokyo (1958)
-Ph. D. in Pharmacy from University of Tokyo
-Currently a professor and the president of the Kitasato Institute of Japan
-Research focuses on the isolation and discovery of microorganisms as well as biologically interesting substances which they produce
Biological diversity of Professor Omura's isolated chemicals(Taken from Microbiological Reviews, 1986, 50, 259.)
Professor Satoshi Omura
Wednesday, May 19, 2004
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
#28Madindolines
#29Macrosphelides
#30Staurosporine
#31Trienomycins
andMycotrienins
NH
Me
Me
O
MeHO
HO
O
SHO2C
AcHN
#32(+)-Lactacystin
#33Pyripyropenes
#34Hitachimycin
#35Purpactins
#36Nafuredin
#37Avermectins
Mike DeMartinoBaran Group Meeting
Professor William Fenical
Biography:
-Born in 1941, Chicago, Illinois
-B.S. in Biochemistry from California State Polytechnic University (1963)
-M.S. in organic chemistry from San Jose State University (1965)
-Ph. D. with professor D. R. Radlick at University of California, Riverside (1969)
-Began at Scripps Institute of Oeanography (SIO) as an assistant professor in 1973
-Became a professor of oceanography at SIO in 1983
-Became Director of Marine Research in 1989
#1Scytalidamides
#2Mangicols
#3Tamandarins
#4Salinamides
William Fenical and Satoshi Omura
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
#6Neomangicols
#7Ningalins
#8Didemninides #9
Neoverrucosane
#10Trichodermamides
#11Pestalone
#12Sterol Glycosides
#13eunicellane diterpenoid; heterogorgiolide
HN
O
O
O
Cl
Me
OH
H
#5Salinosporamide A
HO
OH
Cl
OH
Me
Cl
O
MeOH
O
Me Me
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
#14Arenaric Acid
#15LuisolsA & B
#16Cyclized Didemninide
NNH
Oi-Bu
H
N
NNH
O
Me
OO
NNH
Oi-Bu
H
N
NNH
O
Me
OOH
#17Fumiquinazolines H & I
#18Cyclomarins
Me
MeMe
H
H
O
Me
OMe
O
O
OAcOH
OH
O
O
NN Me
#19Eleutherobin
O
O
Me
O
Me
OH
O
HO
Me
O
O
Me
O
Me
OHHO
Me
#20Octalactins A & B
#21Diazonamides #22
Aspergilloxides
#23Aspergillamides
#24Labiatamides
#25Thraustochytrosides
#26Aplidiamine
#27Polycarpine
Dihydrochloride
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
Isolation of Pestalone-"...potent antibacterial activity aganist drug-resistant bacteria."
-Isolated as yellow crystals (Yes you could just do crystallography, but that's no fun!)
HO
OH
Cl
OH
Me
Cl
O
MeOH
O
Me Me
LREIMS: m/z = 438/440/442->C21 H20 O6 Cl2
-11 Degrees of Unsaturation
IR -Benzaldehyde -Ketone -Hydroxyl groups
UV: Aromatic Ring with extended chromophore
NMRProton: Two olefinic methyl groups One Aromatic resonance methoxy group three exchangable phenols aldehydeCarbon: Alhyde and ketone confirmed Lots of aromatic/vinylic quat carbons One aromatic double
2D NMR: Isoprene Fragment -other modest asignments
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
Me
MeOH
Ph(Me)2COOH
Ti(O-i-Pr)4,(+)-DIPT
82%
Me
MeOH
O
NaH
BnNCO
O NBn
O
OHMeMe
BnN O
O
HO
MeMe
NaHTHF
75% Total
A
AJones
O NBn
O
CO2HMeMe
1. CH2N2
2. KOHEtOH96%
O NBn
O
CO2HMeMe
1. 2N KOH
2. H2, Pd(OH)298% OH
Me
Me
NH2
CO2H
1. HCl(g),MeOH, 100%
2. PhC(OMe)382%
O N
Ph
CO2MeMeMe
1. LHMDS,H2CO, 85%
2. DMSO, DCCO N
Ph
CHOMeMe
CO2Me [Ipc-(+)]2B
O
N
PhMe
MeMeO2C
HO Me
70%, 4:1
1. O3, DMS
2. NaClO2,NaH2PO3
68% O
N
PhMe
MeMeO2C
CO2H
HO MePd,
NH4O2CH NH
MeO2C
MeMe
O
MeHO
HO
1. O.1 N NaOH82%
2. BOPCl, Et3N
79%
AcHNSH
CO2Allyl
NH
MeMe
O
MeHO
HO
O
SAllylO2C
AcHN
Pd(PPh3)4, HCO2H
Et3N, 81% NH
MeMe
O
MeHO
HO
O
SHO2C
AcHN
(+)-Lactacystin
NH
MeMe
O
MeHO
HO
O
SHO2C
AcHN
(+)-Lactacystin
-Total Synthesis of (+)-Lactacystin J. Am. Chem. Soc. 1996, 118, 3584.
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura
TBDPSO
OMPM
MeHO
OMPM
MeOMMTr
OMPM
MeOMMTr
O
O
Me
O
Me
Me
Me
OH
O
HO
Me
O
O
Me
O
Me
Me
Me
OHHO
Me
Octalactin A Octalactin B
1. 9-BBN; H2O2
2. MMTrCl, Base3. TBAF
1. DMP
2. N2CHPO(OMe)2,t-BuOK
1. I2, Morpholine
2. CrCl2 (1.0% w/w NiCl2)
4hr, rt 75-90% (1:1)
TBDPSOCHO
Me
OMPM
MeOMMTrMe
TBDPSO OH
1. H2, Pd/CaCO32. Ac2O, DMAP, py
2. PPTS3. H2, Pd/C
1. DMP;NaClO2
2. K2CO3MeOH
1. 2,2' pyridinedisulfidePPh3;
AgBF4, Refluxing PhMe
63-75%2. TBAF
O
O
MeOH
MPMO
Me
O
O
Me
OH
Me
Me
Me
OTBSMPMO
Me
Me
TBDPSO OAc
Me
OMPM
OHMe
TBDPSO OH
Me
OMPMCO2H
1. DMP
2. CrCl2 (0.1% w/w NiCl2)
74% 1.5:1
I
Me
OTBS
Me
Me
1. DMP2. HF
3. DDQ, H2OO
O
Me
O
Me
Me
Me
OHHO
Me
Octalactin B
1. t-BuOOH, VO(acac)2
2. DMP3. HF
4. DDQ, H2OOctalactin A
-Total Synthesis of Octalins A & B Keith Buszek: J. Am. Chem. Soc. 1994, 116, 5511.
O
O
Me
O
Me
Me
Me
OH
O
HO
Me
Mike DeMartinoBaran Group Meeting William Fenical and Satoshi Omura