The synthesis of alisamycin, nisamycin, LL-C10037 alpha and novel epoxyquinol and epoxyquinone analogues of manumycin A

R J K  Taylor; L  Alcaraz; I  Kapfer-Eyer; G  Macdonald; X D  Wei; N  Lewis

The synthesis of alisamycin, nisamycin, LL-C10037 alpha and novel epoxyquinol and epoxyquinone analogues of manumycin A

R J K Taylor, L Alcaraz, I Kapfer-Eyer, G Macdonald, X D Wei, N Lewis

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Versatile synthetic routes are described for the preparation of a range of epoxyquinol and epoxyquinone analogues of the antitumour antibiotic manumycin A lacking the lower side chain, and these procedures have also been applied to prepare the bioactive natural product LL-C 10037 alpha. The extension of this methodology to provide a general synthetic route to the manumycin family of antibiotics is discussed and exemplified by the first total synthesis of alisamycin and ent-alisamycin. This route includes the novel, stereoselective organometallic addition of the Corey-Wollenberg reagent (E-2-tributylstannylethenyllithium) to the manumycin nucleus and palladium catalysed Stille coupling technology for the introduction of the polyunsaturated 2-amino-3-hydroxycyclopentenone derived amide. Similar methodology has also been employed to complete the first total synthesis of the antibiotic nisamycin.

Original language	English
Pages (from-to)	775-790
Number of pages	16
Journal	SYNTHESIS-STUTTGART
Issue number	5
Publication status	Published - May 1998

Keywords

LL-C10037 alpha
alisamycin
nisamycin
manumycin analogues
Stille coupling
STREPTOMYCES SP K106
ANTITUMOR ANTIBIOTIC LL-C10037-ALPHA
RAS FARNESYLTRANSFERASE INHIBITORS
HYPERVALENT IODINE OXIDATION
ABSOLUTE STEREOCHEMISTRY
STRUCTURE ELUCIDATION
BIOLOGICAL PROPERTIES
METABOLIC PRODUCTS
SODIUM PERBORATE
BIOSYNTHESIS

Cite this

@article{d4deda5243e14e858d1884def1a4d21f,

title = "The synthesis of alisamycin, nisamycin, LL-C10037 alpha and novel epoxyquinol and epoxyquinone analogues of manumycin A",

abstract = "Versatile synthetic routes are described for the preparation of a range of epoxyquinol and epoxyquinone analogues of the antitumour antibiotic manumycin A lacking the lower side chain, and these procedures have also been applied to prepare the bioactive natural product LL-C 10037 alpha. The extension of this methodology to provide a general synthetic route to the manumycin family of antibiotics is discussed and exemplified by the first total synthesis of alisamycin and ent-alisamycin. This route includes the novel, stereoselective organometallic addition of the Corey-Wollenberg reagent (E-2-tributylstannylethenyllithium) to the manumycin nucleus and palladium catalysed Stille coupling technology for the introduction of the polyunsaturated 2-amino-3-hydroxycyclopentenone derived amide. Similar methodology has also been employed to complete the first total synthesis of the antibiotic nisamycin.",

keywords = "LL-C10037 alpha, alisamycin, nisamycin, manumycin analogues, Stille coupling, STREPTOMYCES SP K106, ANTITUMOR ANTIBIOTIC LL-C10037-ALPHA, RAS FARNESYLTRANSFERASE INHIBITORS, HYPERVALENT IODINE OXIDATION, ABSOLUTE STEREOCHEMISTRY, STRUCTURE ELUCIDATION, BIOLOGICAL PROPERTIES, METABOLIC PRODUCTS, SODIUM PERBORATE, BIOSYNTHESIS",

author = "Taylor, {R J K} and L Alcaraz and I Kapfer-Eyer and G Macdonald and Wei, {X D} and N Lewis",

year = "1998",

month = may,

language = "English",

pages = "775--790",

journal = "SYNTHESIS-STUTTGART",

issn = "0039-7881",

publisher = "Georg Thieme Verlag",

number = "5",

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TY - JOUR

T1 - The synthesis of alisamycin, nisamycin, LL-C10037 alpha and novel epoxyquinol and epoxyquinone analogues of manumycin A

AU - Taylor, R J K

AU - Alcaraz, L

AU - Kapfer-Eyer, I

AU - Macdonald, G

AU - Wei, X D

AU - Lewis, N

PY - 1998/5

Y1 - 1998/5

N2 - Versatile synthetic routes are described for the preparation of a range of epoxyquinol and epoxyquinone analogues of the antitumour antibiotic manumycin A lacking the lower side chain, and these procedures have also been applied to prepare the bioactive natural product LL-C 10037 alpha. The extension of this methodology to provide a general synthetic route to the manumycin family of antibiotics is discussed and exemplified by the first total synthesis of alisamycin and ent-alisamycin. This route includes the novel, stereoselective organometallic addition of the Corey-Wollenberg reagent (E-2-tributylstannylethenyllithium) to the manumycin nucleus and palladium catalysed Stille coupling technology for the introduction of the polyunsaturated 2-amino-3-hydroxycyclopentenone derived amide. Similar methodology has also been employed to complete the first total synthesis of the antibiotic nisamycin.

AB - Versatile synthetic routes are described for the preparation of a range of epoxyquinol and epoxyquinone analogues of the antitumour antibiotic manumycin A lacking the lower side chain, and these procedures have also been applied to prepare the bioactive natural product LL-C 10037 alpha. The extension of this methodology to provide a general synthetic route to the manumycin family of antibiotics is discussed and exemplified by the first total synthesis of alisamycin and ent-alisamycin. This route includes the novel, stereoselective organometallic addition of the Corey-Wollenberg reagent (E-2-tributylstannylethenyllithium) to the manumycin nucleus and palladium catalysed Stille coupling technology for the introduction of the polyunsaturated 2-amino-3-hydroxycyclopentenone derived amide. Similar methodology has also been employed to complete the first total synthesis of the antibiotic nisamycin.

KW - LL-C10037 alpha

KW - alisamycin

KW - nisamycin

KW - manumycin analogues

KW - Stille coupling

KW - STREPTOMYCES SP K106

KW - ANTITUMOR ANTIBIOTIC LL-C10037-ALPHA

KW - RAS FARNESYLTRANSFERASE INHIBITORS

KW - HYPERVALENT IODINE OXIDATION

KW - ABSOLUTE STEREOCHEMISTRY

KW - STRUCTURE ELUCIDATION

KW - BIOLOGICAL PROPERTIES

KW - METABOLIC PRODUCTS

KW - SODIUM PERBORATE

KW - BIOSYNTHESIS

M3 - Article

SN - 0039-7881

SP - 775

EP - 790

JO - SYNTHESIS-STUTTGART

JF - SYNTHESIS-STUTTGART

IS - 5

ER -