JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16

Journal of the American Chemical Society - 1977, Volume 99

Editor - Cheves WallingNumber of Issues: 26Number of Articles: 2,394Number of Pages: 8,648Total Syntheses Published: 51

Most Cited Articles:

Dewar, M.J., et al. "Ground States of Molecules. 38. The MNDO Method. Approximations and Parameters" (1926 citations)

Kalyanasundaram, K., et al. "Environmental Effects on Vibronic Band Intensities in Pyrene Monomer Fluorescence and their Applications in Studies of Micellar Systems" (1921 citations)

Allinger, Norman L. "Conformational Analysis. 130. MM2. A Hydrocarbon Force Field Utilizing V1 and V2 Torsional Terms" (1831 citations)

Noteworthy Happenings in the World of Science:

- Nobel Prize in Chemistry: Ilya Prigogine "for his contributions to non-equilibrium thermodynamics, particularly the theory of dissipative structures".

- Legionella bacteria, previously an unknown organism, are linked to Legionnaires' Disease.

- Insulin is made in the lab from bacteria by "gene splicing."

- The last natural case of smallpox is discovered in a small Somalian village.

- The rings of Uranus are discovered

Sports, Politics, Religion - The New York Yankees defeat the Los Angeles Dodgers to win their 21st World Series

- President Jimmy Carter pardons Vietnam War draft evaders

- United States Federal Debt = $706.4 billion

- Harvey Milk is elected as the first openly homosexual politican in San Francisco

- The WAVES are disbanded, formally allowing women to join to U.S. Navy

The World Outside of ScienceNewsworthy Events of 1977

Apple Computer is incorporatedApple II Series is released

Space Mountain opensat Disnetland

American Roy Sullivan is struck by lightning for the seventh time

New York City endures a 25-hour blackout Elvis Presley dies at age 42 Atari releases its "Video

Computer System"The Soundtrack of 1977

Movies of 1977

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16

"Kinetically Controlled Total Syntheses of dl-Trachelanthamidine and dl-Isoretronecanol"Danishefsky, McKee, and Singh; JACS 1977, 99, 4783-4788

An interesting use of their recent methods. First, let's review...Previous Investigations into nucelophilic cyclopropane ring-opening:

CO2Et

CO2Et

R

Nu CO2Et

CO2Et

R

Nu

Harsh conditions to open cyclopropanes, even in the presence of activating groups, has not allowed their synthetic utility to be fully realized.

R = alkyl, vinyl

It was observed that both esters can participate in charge delocalization of the emerging carbanion when the plane of the cyclopropane is orthoganol to the C=O and -OR ester plane.

This orientation is however unrealistic due to large steric interactions.

Solution:

O

O MeMe

O

O

H2, Pd/C

O OR

OR

O

"Spiroactivation"

O

O MeMe

O

O piperidine,RT

O

O MeMe

O

O

HN

pyridineRT

(99%)

(99%)(92%)

O

O MeMe

O

ON

PhNH2O

O MeMe

O

ONHPh

(99%)

NPh

CO2H

O

"Kinetic reactivity due to conformationally defined overlap."

Applications to total synthesis of recine bases:JACS 1975, 97, 3239-3241

N

HO

OHH

trachelanthamidine

N

HO

OHH

isoretronecanolN

HO

OHH

N

HO

OHHHO

HO

hastanecine

dihydroxyheliotridaneJACS 1977, 99, 7711-7713

)(

"Total Synthesis of dl-Lycoramine"Schultz, Yee, and Berger; JACS 1977, 99, 8065-8067

O

OH

OMe

(±)-lycoramine

- Galanthamine-type alkaloid found in plants of the Amarylidaceae- Synthesis plan relied on a novel construction of benzodifurans:

Selected further reading: JOC 1982, 47, 1513-1518 (Bischler-Napieralsky)JOC 1993, 58, 3877-3885 (radical cyclization); OL 2012, 14, 2714-2717 (Heck cyclization)

NMe

See also: E. Cherney GM 05/12/12J. Gallagher GM 02/18/04

O

RO

O

R

OArO

O

Total synthesis:OEt

O

1) (OEt)2POCH2CN2) LAH3) ClCO2Me4) H2SO4

(76%)

ONHCO2Me

H2O2(70%)

ONHCO2Me

OOH

OMe

MeO2C (1 eq)

KOH (1 eq)18-crown-6 (1 eq)

(50%)

OMe

CO2Me

OO

NH

MeO2C

O

OMe

CO2Me

OO

NH

MeO2C

hν

OO

H

OMe

CO2MeHN CO2Me

OO OMe

CO2MeHN CO2Me

1) CH(OMe)32) LAH(86%, 3 steps)

O OMe

CO2HNHMe

MeO OMe

1) SOCl2-Et3N(2 eq)2) H2SO4(76%)

O OMe

O

NMe

1) LTMP2) (SPh)2SO2

3) LAH4) MsCl

(70%)O OMe

NMe

OMsPhS

PhS1) HgOHgCl22) CrCl2(85%)

O OMe

NMe

O

LAH

O OMe

NMe

"The developed photocylization reaction respresents a general method for synthesis of complex aryl annelated dihydrofurans"

PhtHN

OPhtHN

O

CO2Me

OO

MeO2C

JACS 1977, 99, 4783-4788

CO2Me

OOPhtHN

OTHP

O O

OTHP

NHPht

CO2Me

Access to cyclopropane precursors was generally straightforward.For example, A was prepared over 6 steps, 24% yield

(A)

(110º, 20 h, 10%)TL 1966, 4421

(±)-lycoramine

HO

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16"Applications of [2,3]-Sigmatropic Rearrangements to Natural Product Synthesis.

The Total Synthesis of (±)-Bakkenolide-A (Fukinanolide)"Evans, Sims, and Andrews; JACS 1977, 99, 5453-5461

OO

Me Me

(±)-bakkenolide-A

OMe

H

MeO Me

H

MeYX

Me

Me

H

MeMe

X Y

[2,3]

O

Me

H

Me"At the onset of this study, no precedent existed for the stereochemistry of [2,3]-sigmatropic rearrangements such as that illustrated by the above transformation"

7

7

Stereochemistry of [2,3]-sigmatropic rearrangement - model study:

tBu

SPh

X

tBu

SX

Ph

tBu tBuX SPhX SPh

+

equitorial axial

X: eq:axCCl2 97:3

CHCO2Et 91:9O 92:8

Steric factors play a significant role in the preference for the migrating group to be equitorial.Equitorial preference is also maintained when oxygen is the migrating group's terminus.

Retrosynthetic Analysis:

MeMe

O

SnBu

KOtBu(84%)

O

SnBu

MeMe

(5:1 dr)

1) KOH2) OsO4,NaIO4(70%)

O O

MeMe

O

MeMe

H

1) KOtBu2) H2, Pd/C

(59%)

Li(60%)

MeMe

HHO

1) PBr32) NaH,

A(75%)

NH

HNTs CS2Me(A)

MeMe

HS

SMeN

TsHN

1)NaH2) HgOHg2Cl2(62%)

MeMe

H

MeSO

single diastereomer

H2SeO3(39%)

OMeMe

H

O

(±)-bakkenolide-A

Total Synthesis of (±)-bakkenolide-A

Isolation & Characterization:Tett. Lett. 1968, 9, 369Chem Ind. 1968, 60, 318Phytochem. 1976, 15, 1713

Bakkenolides (synthetic studies):JOC 1985, 50, 3943-3945Tett. Lett. 1988, 29, 5661-5662Org. Lett. 1999, 1, 663-666

Further Reading:[2,3]-sigmatropic rearrangements:

JACS 1996, 118, 7513-7528ACIE 2000, 39, 3740-3742

Org. Lett. 2005, 7, 1629-1631

"A Stereoselective Total Synthesis of Estrone by an Intramolecular Cycloaddition Reaction of Olefinic o-Quinodimethane"

Kametani, Nemoto, Ishikawa, Shiroyama, Matsumoto, and Fukumoto; JACS 1977, 99, 3461-3466

Me

NC

OMe

MeO2C

Δ

OMe

MeMeO2C

CN

OMe

CN

HMeO2C Me

HO

Me

H

HH

O

EstronePrevious finding:

Heterocycles 1976, 4, 241

MeO

CNConvergent total synthesis:

Br OTHP

NaNH2, NH3(91%) MeO

EtOTHPCN

1) Na, NH32) HCl(79%) MeO

OH

1) TsCl, py2) NaI(40%)

MeO

OMe MgBr

CuI(66%)

OMe

+

KOtButBuOH(17%)

OMe S

nBu1) NaH, HCO2Et2) TsOH,nBu-SH(62%)

MeO

OMe

SnBu

KOH(45%)

MeO

OMeO

MeO

Δ

then py•HCl(76%)

HOH

H

Me

H

O

MeO

OMe

HH

H

O Me

HH

MeOd-Homoestrone

Explanation of stereoselectivity:

exo-T.S. endo-T.S.

Female sex hormone has garnered much attention from the synthesis community. Precursor to 19-norsteroid (contraceptive).

Selected further reading:JACS 1952, 74, 2832-2849JOC 1963, 28, 1092-1094JACS 1973, 95, 7501-7502JACS 1975, 97, 380-387Y. See GM - 08/23/2014

Target was pursued as a means to develop methods pertaining to cycloadditions based on o-quinodimethanes

I

Cl

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16

N

O

OMe

H2NO

NH2O

OMe

NMe

Nakatsubo, Fukuyama, Cocuzza, and Kishi; JACS 1977, 99, 8815-8816

"Synthetic Studies toward Mitomycins.2. Total Synthesis of dl-Porfiromycin."

(±)-porfiromycin

- Member of the mitomycin antibiotic class- Structures of mitomycins were first elucidated in 1962- Broad spectrum antibiotic, also reported antitumor- Several reports towards synthetic mitomycins

JOC 1974, 39, 3739Tetrahedron Lett. 1974, 3283Can. J. Chem. 1975, 53, 960Windholz, M., Ed., The Merck Index, 9th Edition (1976)

The first total synthesis of (±)-porfiromycin

MeO

MeO

OBn

OBn

SMeSMe

CN

OAc1) NaOMe2) BnBr, KH3) HgCl2(85%)

MeO

MeO

OBn

OBn

OMeOMe

CN

OBn1) LDA2) PhSeBr3) H2O2(77%)

MeO

MeO

OBn

OBn

OMeOMe

CN

OBn1) DIBAL2) NaBH43) Ac2O-py4) OsO4(75%)

MeO

MeO

OBn

OBn

OMeOMe

OBn

OAc

HO OH

1) MsCl, Et3N2) NaH, DMF3) NaOMe, MeOH

(93%)

MeO

MeO

OBn

OBn

OMeOMe

OBn

OHO

1) LiN32) Ms2O3) BnNH24) BnBr(51%)

MeO

MeO

OBn

OBn

OMeOMe

OBn

NBn2

MsON3

1) P(OMe)32) NaH3) LAH4) MeI, K2CO3 (47%)

MeO

MeO

OBn

OBn

OMeOMe

OBn

NBn2

MeN

1) H2, Pd/C2) O2

(40%)

MeO

MeO

O

OHN

NMe

OH1) [Ph3C][BF4]2) COCl2, PhNMe23) NH3(76%)

N

O

OMe

MeOOCONH2

OMe

NMeNH3 / MeOH

N

O

OMe

H2NOCONH2

OMe

NMe

"Total Synthesis of Arborine, Glycosamine, and Rutecaprine by Consensation of Iminoketene with Amides"

Kametani, Loc, Higa, Koizumi, Ihara, and FukumotoJACS 1977, 99, 2306-2309Recent findings:

CO2H

NH2

SOCl2

O

OSN

HO

•O

NH N

N

ON

MeO

The authors hypothesize a stepwise mechanism and envision formation of quinazolones by reaction of iminoketenes with amides

JACS 1976, 99, 6186

Proof of concept:

O

OSN

HO

HN

ON

N

O - Convenient synthesis of a quinazolone - A simple total synthesis of an alkaloid found in nature in Mackinlaya (bonus!)

More alkaloids:O

OSN

HO

CONH2Ph

(82%)

(40%) N

NH

O

Ph

- Acyclic amides lend themselves to this methodology

- Short total synthesis of glycosamine

HN

HN CHO

+

benzene, 2 h, RT(63%)

NH

N

N

O

NH

N

N

OHClAcOH

air110º C7 days(45%)

R R'

OEtO P

O

EtO OtBu

CN+ NaH R

R' OtBu

CN ZnCl2Ac2O

R

R' OAc

CN

R R'

XOWatt, D.S., and co-workers; JACS 1977, 99, 182-186

glycosamine

rutaecarpine

"A One-Carbon Homologation of Carbonyl Compounds to Carboxylic Acids, Esters, and Amides"

For more fun with ketenes, see H. Dao GM 01/21/2014

base

"Carboxylic acids, esters, and amides are accessed by treatment of acetoxyacrylonitriles with KOH (aq), sodium alkoxides, and amines, respectively."

OMeOMe

R = alkyl,aryl

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16"Allylic Oxidation of Olefins by Catalytic and Stoichiometric

Selenium Dioxide with tert-Butyl Hydroperoxide"Umbreit, M.A., and Sharpless, K.B.; JACS 1977, 99, 5526-5528

Problem: allylic oxidation using stoichiometric selenium often requires difficult removal of

colloidal reduced selenium species

Solution: reoxidation with alkyl peroxides gives clean allylic oxidation and allows for catalytic (1.5-2.0 mol%) selenium

R

SeO2 (1.5 mol%)t-BuOOH (4 eq)

salicylic acid (cat.)(50-90%)

R

OH R = alkyl, cycloalkyl, aryl

overoxidation does not predominate

"Conjugate Addition of Vinylcopper Complexes Derived from Addition of Alkylcopper Complexes to Acetylenes. A Sterespecific Synthesis of Trisubstituted Olefins."

Marfat, McGuirk, Kramer, and HelquistJACS 1977, 99, 253-255

R3MgBr 1) [(Me)2S]CuBr

C CHR4

2)R2

O

R13)4) NH4Cl (aq) R4 R2

OR1R3

R4

R3[Cu]

Forming the copper complex:

R3MgBr[(Me)2S]CuBr

Overall transformation:

ether, Me2S-45º C, 1.5 h

R3Cu[(Me)2S]•MgBr2

C CHR4

-25º C, 2 h R4

R3Cu[(Me)2S]•MgBr2

R3, R4 = n-alkylPurification of the dimethylsulfide-cuprous bromide complex is crucial to avoiding side reactions(see House, H.O. Acc. Chem Res., 1975, 40, 1460)

Copper complex readily add to various Michael acceptors:

O

Ph Ph

O

Ph Me

O O O O

(70%) (52%) (53%) (30%) (62%)

- Stereochemical outcome is highly dependent on substrate- Ratio of (E) and (Z) isomers strongly typically very high (> 99:1)- Carbonyl in product easily amenable to further transformations

"Hydroacylation of Michael Acceptors through Sequential Insertion Reactions of Organocarbonylferrates"

Cooke, M.P., and Parlman, R.M.; JACS 1977, 99, 5222-5224

RX Na2Fe(CO)4 R Fe(CO)4CO2Et

then HR CO2Et

"Relatively few methods exist to introduce acyl units in a conjugate manner into Michael acceptors."

Alkylated iron carbonyl complex undergoes sequential insertions:

R Fe(CO)4

EtO2C

R Fe(CO)3

O

EtO2C

R

O

Fe(CO)3

CO2Et

H

R CO2Et

OA variety of Michael acceptors, including linear, cyclic, branched, and substituted tolerate the reaction conditions and give high yields

Selected examples:

Br

Na2Fe(CO)4THF

CO2Et

1)

2)then AcOH O

CO2Et

(92%)

I

Na2Fe(CO)4THF

1)

2)then AcOH

(94%)

O

O

O

INa2Fe(CO)4THF

1)

2)then AcOH

(95%)CN O

CN

I CO2Et

Na2Fe(CO)4THFthen AcOH

(85%)

OCO2Et

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16

N NH

HN NHHOHO

H2N

NH2

O NH2

O

"A Stereospecific Total Synthesis of dl-Saxitoxin"

(±)-saxitoxin

Tanino, Nakata, Kaneko, and Kishi; JACS, 1977, 99, 2818-2819

Shellfish poison isolated in 1957 (Alaskan Butter Clam)Structure solved by x-ray in 1975

One of most lethal non-protein poisons known Potent and specific sodium channel clocker

Used in nerve disorder research and as a chemical weaponJACS 1957, 79, 5230-5235JACS 1975, 97, 1238-1239JACS 1975, 97, 6008-6012

N

O

O

CO2Me

O

1) propylene glycol,TsOH, PhMe2) H2NNH2, MeOH(74%)

HN

O

O

OHN

O

O

MeO2C1) P4S102) A

Me

OCO2Me

Br

3) NaHCO3(50%)

BzO CHOSi(NCS)4

HN

NSO

OCO2Me

CH2OBz

HN

NSO

ONHCONH2 1) H2NNH2

2) NOCl; Δ3) NH3(75%)

1) HS(CH2)3SH,BF3•OEt2

N NH

HN NHSS

O

S

2) AcOH, TFA(50%)

N NH

HN NHSS

H2N

NH2

1) Et3OBF4NaHCO32) EtCO2NH4(33%)

1) BCl32) NBS; Δ(23%) N NH

HN NHHOHO

H2N

NH2

2) H2O, Δ N NH

HN NHHOHO

H2N

NH2

OHO

O

NH2

Cl S NCO1) OO

OBzOBz

OBz

(50%)

Dedicated to Professor R.B. Woodward on the occasion of his 60th birthday.

(±)-saxitoxin17 steps

Further reading:Kishi, et al. JOC 1983, 48, 3833-3835 (improved route to precursor)Jacobi, et al. JACS 1984, 106, 5594-5598 (formal synthesis)Kishi, et al. JACS 1992, 114, 7001-7006 ((-)-decarbamoylsaxitoxin)DuBois, et al. JACS 2006, 128, 3926-3927 ((+)-saxitoxin)Nagasawa, et al. ACIE 2007, 46, 8625-8628 ((-)-decarbamoylsaxitoxin)Nagasawa, et al. ACIE 2016, 55, 11600-11603 (11-saxitoxinethanoic acid)

Challenges overcome:Highly functionalized and sensitive to oxidationTricyclic core dense with heteroatomsDicationic nature makes for purification challenges

"Nuclear Analogs of β-Lactam Antibiotics"Huffman, Holden, Buckley, Gleason, and Wu; JACS 1977, 99, 2352-2355

NOMe

ODMB

O

ON3 CF3

O+

1. The Total Synthesis of a 7-Oxo-1,3-diazabicyclo[3.2.0]heptane-2-carboxylic acid via a Versatile Monocyclic Intermediate

Et3N(58%) N

O DMB

N3 CO2Me 1) H2, Pd/C2) PhOCH2COCl,Et3N(84%)

NO DMB

HN CO2Me

O

PhO

NHO

HN CO2Me

OK2S2O8

Na2HPO4NHO

HN

O

OPh

(69%)

NHO

HN

O

OPh

H2N

N CO2Bz

AcCl, py

(20%)

benzyl glyoxylate(65%)

NO

HN

O

OPh

NAc

H

CO2H

then H2, Pd/C

(1)

Biological evaluation of (2):Pathogen MIC (µg/mL)

S. aureus 100S. paradyssenteriae 400

B. subtilis 10

OPh

2. The Total Synthesis of 8-Oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acids

NHO

HN

O

R

5 steps(40%)

HS

NO

HN

O

RS

HO CO2CH(Ph)2

thiol alkylation N

S

OOS

H H

CO2H

Me OtBu

O

O

Br

(7 steps from 1)

(2)

1) SOCl2, py2) TFA (3)

14% yield,10 steps from (1)

N

R = thienyl

R = OPh

S

O Me

HN

O

OPhH

HO CO2tBu

TFAA, py NS

O Me

HN

O

OPhH

CO2RR = t-Bu (4)R = H (5)

1) NBS, AIBN2) KOAc, 18-crown-6

NS

O

HN

O

OPhH

CO2RR = t-Bu (6)R = H (7)

OAcOne synthetic sequence provided a range of novel synthetic β-Lactams for biological evaluation.

All synthesized analogs displayed "good antibacterial activity" against B. subtilis and penicillin-resistant S. aureus.

Additionally, 3 displayed higher activity against gram-negative pathogens than naturally obtained cephalosporins

(A)

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16

O

OO H

OHH

OVernolepin

O

O H

OO

OHH

Vernomenin

"The Total Synthesis of dl-Vernolepin and dl-Vernomenin"Danishefsky, Schuda, Kitahara, and Etheredge; JACS 1977, 99, 6066-6075

Further reading:Iio, et al. Tetrahedron, 1979, 35, 941-948; Zutterman, et al. Tetrahedron 1979, 35, 2389-2396

O

O

O O

H

OH

Y O

OH

OO

O

Y

H6

7 6 7

O

OH

CHO

OO

OH

O

H

OH

OOH CO2Me

6

7

7

6

Isolated in 1968 from dried fruit of Vernonia amygdalinaJACS 1968, 90, 3596

Displayed in vitro tumor cytotoxicity against human carcinoma of the nasal

pharanx (1.80 µg/mL )JMC 1971, 14, 1147

Previous work: Grieco's Approaches to the AB-ring; total synthesis

O

O H

OtBuMeS

NOH H

HO2C

OtBu

H8 steps total

O

OHJOC, 1975, 40, 1450-1453

OMe

OO

O H

JACS, 1976, 98, 1612–1613; Tett. Lett. 1975, 48, 4213-4216;OMe

OAcH

OAc

OCO2Me

O

H

OH

OO

O

O

OO H

OHH

O(±)-vernolepin20 total stepsSee also: Grieco, et al. JACS 1977, 99, 5773-5780

+

OMe

TMSO

CO2MeCO2Me

HO

O

OO H

OHH

O

(92%)

Danishefsky's Total Synthesis: an orthoganol approach to the precursor

3) DBU(87%, 3 steps)

1) NaOH;2) I2, KI

1) NaOH2) m-CPBA3) NaOAc,Ac2O

O H

O

O

O

mesitylene100 h, reflux

(76%) O H

O

O

(76%)

1) OsO4,2) Pb(OAc)4

3) LiAl(OtBu)3H;then Amberlite

O

O H

O

O

O

1) ethylene glycol,

MgSO4, TsOH

2) DIBAL-H(62%)

"Unprecedented orthoester formation from δ-lactone"

O

OH

CHO OH

67

O

OHO

O

OAc

67

Ph3P CH21)2) Ac2O, py

(87%)

Problem: How to effect nucelophilic ring-opening selectively at C7 position?

see also: JACS 1976, 98, 3208-3230

Equitorial orientation favored, but blocked

from nucelophilic attack

Disfavored axial arrangement,

reactive conformation

1) LiCH2CO2Li2) H+

3) CH2N2

H3O+

O

OO H

OHH

O

(56%)

(±)-vernolepin19 total steps

1) LDA,H2C NMe2

2) H+

O

OO H

OHH

OMe2N

NaHCO3

Danishefsky's Endgame - Selective ring-opening; lactonization

O

O

JACS: Year in Review: 1977Tom Stratton Baran Group Meeting - 10/22/16

Syntheses not covered:

OMeHOH

HH

Me

Me11a-hydroxyprogesterone

Johnson, W.S., et al. JACS 1977, 99, 8341-8343

Me

Me O

Me

O

(±)-acorgermacrone (±)-preisocalamendiolStill, C.W., et al.

JACS 1977, 99, 4186-4187

O

O

O

OMeH

HO

Me

Me

(±)-LL-Z1271αWelch, S.C., et al.

JACS 1977, 99, 549-556

N

OMe

CO2H

MeMe

O

MeMe

OHO

OHMeO

O

MeMe

OHO

OH

MeO

OMe

Illudinine Illudalic acid Illudacetalic acidWoodward, R.B., Hoye, T.R.; JACS 1977, 99, 8007, 8014

MeMe

Me

Me

humuleneGrubbs, R. H., et al.

JACS 1977, 99, 3864-3867

NHHN

O

S

H HCO2H4

d-biotinConfalone, P.N., et al.

JACS 1977, 99, 7020-7026

OMe

Me

O

H

H

(±)-frullanolideStill, C.W., et al.

JACS 1977, 99, 948-950

OO

OMeOMe OMeOMe

AcOMe Mekadsurin

Ghera, et al.JACS 1977, 99, 7673-7678

N

HO

HOH

Me

HH

H

H

H

H

OHMe

H

Me

verticineKutney, et al.

JACS 1977, 99, 964-966

O

O

O

NH2

(±)-ceruleninBoeckman, R.K., et al.

JACS 1977, 99, 2805, 2806

HO

CO2Na

OCO2Na

disodium prenphenateDanishefsky, et al.

JACS 1977, 99, 7740-7741

O

O

Me

Me CO2H(±)-methylenomycin A

Smith, A.B., et al. JACS 1977, 99, 7085-7087