Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin with use of asymmetric anti- and syn-glycolate aldol reactions

被引：71

作者：

Andrus, MB ^{[1
]}

Meredith, EL ^{[1
]}

Simmons, BL ^{[1
]}

Sekhar, BBVS ^{[1
]}

Hicken, EJ ^{[1
]}

机构：

[1] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA

来源：

ORGANIC LETTERS | 2002年 / 4卷 / 20期

关键词：

D O I：

10.1021/ol0267432

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Geldanamycin (GA), an antitumor Hsp90 inhibitor, was made for the first time by using an oxidative demethylation reaction as the final step. A biaryldioxanone auxiliary set the anti C11-12 hydroxy-methoxy functionality and a methylglycolate auxiliary based on norephedrine was used for the syn C6-7 methoxy-urethane. p-Quinone-forming oxidants, CAN and AgO, produced an unusual aza-quinone product. Nitric acid gave GA from a trimethoxy precursor in 55% yield as a 1:10 mixture with nonnatural o-quino-GA.

引用

页码：3549 / 3552

页数：4

共 32 条

[1] Boron-mediated double aldol reaction of carboxylic esters [J].

Abiko, A ;

Liu, JF ;

Buske, DC ;

Moriyama, S ;

Masamune, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (30) :7168-7169

[2] The anti-selective boron-mediated asymmetric aldol reaction of carboxylic esters [J].

Abiko, A ;

Liu, JF ;

Masamune, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (10) :2586-2587

[3] Glycolate aldol reactions with boron enolates of bis-4-methoxyphenyl dioxanone [J].

Andrus, MB ;

Mendenhall, KG ;

Meredith, EL ;

Sekhar, BBVS .

TETRAHEDRON LETTERS, 2002, 43 (10) :1789-1792

[4] Synthesis of the left-hand portion of geldanamycin using an anti glycolate aldol reaction [J].

Andrus, MB ;

Meredith, EL ;

Sekhar, BBVS .

ORGANIC LETTERS, 2001, 3 (02) :259-262

[5] Highly selective syn glycolate aldol reactions with boron enolates of Masamune norephedrine esters [J].

Andrus, MB ;

Sekhar, BBVS ;

Turner, TM ;

Meredith, EL .

TETRAHEDRON LETTERS, 2001, 42 (41) :7197-7201

[6] Anti-selective glycolate aldol additions with an oxapyrone boron enolate [J].

Andrus, MB ;

Sekhar, BBVS ;

Meredith, EL ;

Dalley, NK .

ORGANIC LETTERS, 2000, 2 (19) :3035-3037

[7] TOTAL SYNTHESIS OF (+)-MACBECIN-I [J].

BAKER, R ;

CASTRO, JL .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1990, (01) :47-65

[8] GELDANAMYCIN, A NEW ANTIBIOTIC [J].

DEBOER, C ;

MEULMAN, PA ;

WNUK, RJ ;

PETERSON, DH .

JOURNAL OF ANTIBIOTICS, 1970, 23 (09) :442-&

[9] ASYMMETRIC-SYNTHESIS OF THE BENZOQUINOID ANSAMYCIN ANTITUMOR ANTIBIOTICS - TOTAL SYNTHESIS OF (+)-MACBECIN [J].

EVANS, DA ;

MILLER, SJ ;

ENNIS, MD .

JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (02) :471-485

[10] ARTIFICIAL PHOTOSYNTHESIS OF BETA-KETOCARBOXYLIC ACIDS FROM CARBON-DIOXIDE AND KETONES VIA ENOLATE COMPLEXES OF ALUMINUM PORPHYRIN [J].

HIRAI, Y ;

AIDA, T ;

INOUE, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (08) :3062-3063

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