A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products

A  Lewis; I  Stefanuti; S A  Swain; S A  Smith; R J K  Taylor

A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products

A Lewis, I Stefanuti, S A Swain, S A Smith, R J K Taylor

Chemistry

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

Abstract

A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) Useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.

Original language	English
Pages (from-to)	104-116
Number of pages	13
Journal	Organic and Biomolecular Chemistry
Volume	1
Issue number	1
Publication status	Published - 7 Jan 2003

Keywords

CHONDROMYCES SPECIES MYXOBACTERIA
ENANTIOSELECTIVE TOTAL SYNTHESIS
RING-CLOSING-METATHESIS
NATURAL-PRODUCTS
CYTOTOXIC MACROLIDES
MAGNESIUM EXCHANGE
COUPLING REACTIONS
GRIGNARD-REAGENTS
CORE STRUCTURE
OXIMIDINE-II

Cite this

@article{901f10e033794b5c8bf2fa456190c7d5,

title = "A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products",

abstract = "A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) Useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.",

keywords = "CHONDROMYCES SPECIES MYXOBACTERIA, ENANTIOSELECTIVE TOTAL SYNTHESIS, RING-CLOSING-METATHESIS, NATURAL-PRODUCTS, CYTOTOXIC MACROLIDES, MAGNESIUM EXCHANGE, COUPLING REACTIONS, GRIGNARD-REAGENTS, CORE STRUCTURE, OXIMIDINE-II",

author = "A Lewis and I Stefanuti and Swain, {S A} and Smith, {S A} and Taylor, {R J K}",

year = "2003",

month = jan,

day = "7",

language = "English",

volume = "1",

pages = "104--116",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "The Royal Society of Chemistry",

number = "1",

}

TY - JOUR

T1 - A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products

AU - Lewis, A

AU - Stefanuti, I

AU - Swain, S A

AU - Smith, S A

AU - Taylor, R J K

PY - 2003/1/7

Y1 - 2003/1/7

N2 - A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) Useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.

AB - A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) Useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.

KW - CHONDROMYCES SPECIES MYXOBACTERIA

KW - ENANTIOSELECTIVE TOTAL SYNTHESIS

KW - RING-CLOSING-METATHESIS

KW - NATURAL-PRODUCTS

KW - CYTOTOXIC MACROLIDES

KW - MAGNESIUM EXCHANGE

KW - COUPLING REACTIONS

KW - GRIGNARD-REAGENTS

KW - CORE STRUCTURE

KW - OXIMIDINE-II

M3 - Article

SN - 1477-0520

VL - 1

SP - 104

EP - 116

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 1

ER -