A spontaneous bicyclization facilitates a synthesis of (-)-hispidospermidin

Junko Tamiya; Erik J. Sorensen

doi:10.1016/S0040-4020(03)00936-0

A spontaneous bicyclization facilitates a synthesis of (-)-hispidospermidin

Junko Tamiya, Erik J. Sorensen

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13 Scopus citations

Abstract

A concise, enantiospecific synthesis of the phospholipase C inhibitor (-)-hispidospermidin (1) has been achieved by approximating the architecture of a reactive intermediate that may lie on the biosynthetic pathway leading to this natural product. Two compounds derived from (R)-(+)-pulegone were joined by a highly diastereoselective carbonyl addition. A proximity-facilitated, acid-induced bicyclization of spiro[4.5]deca-1,7-diene 29 gave rise to the tetracyclic framework of 1 and was the key transformation in this synthesis.

Original language	English (US)
Pages (from-to)	6921-6932
Number of pages	12
Journal	Tetrahedron
Volume	59
Issue number	35
DOIs	https://doi.org/10.1016/S0040-4020(03)00936-0
State	Published - Aug 25 2003
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Drug Discovery
Organic Chemistry

Keywords

Biomimetic synthesis
Hispidospermidin
Proximity
π-cyclization

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10.1016/S0040-4020(03)00936-0

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title = "A spontaneous bicyclization facilitates a synthesis of (-)-hispidospermidin",

abstract = "A concise, enantiospecific synthesis of the phospholipase C inhibitor (-)-hispidospermidin (1) has been achieved by approximating the architecture of a reactive intermediate that may lie on the biosynthetic pathway leading to this natural product. Two compounds derived from (R)-(+)-pulegone were joined by a highly diastereoselective carbonyl addition. A proximity-facilitated, acid-induced bicyclization of spiro[4.5]deca-1,7-diene 29 gave rise to the tetracyclic framework of 1 and was the key transformation in this synthesis.",

keywords = "Biomimetic synthesis, Hispidospermidin, Proximity, π-cyclization",

author = "Junko Tamiya and Sorensen, \{Erik J.\}",

note = "Funding Information: We thank The Skaggs Institute for Chemical Biology at TSRI, a Graduate Research Fellowship to J. T. (Abbott Laboratories), a Beckman Young Investigator Award to E. J. S., and a grant from the Merck Research Laboratories for their generous support of this research. We thank Professor Larry Overman and Dr. Adam Tomasi for samples of natural and synthetic (−)-hispidospermidin and helpful discussions. We also thank Professor Robin Polt for bringing the pioneering studies of A. McKenzie to our attention.",

year = "2003",

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doi = "10.1016/S0040-4020(03)00936-0",

language = "English (US)",

volume = "59",

pages = "6921--6932",

journal = "Tetrahedron",

issn = "0040-4020",

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number = "35",

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T1 - A spontaneous bicyclization facilitates a synthesis of (-)-hispidospermidin

AU - Tamiya, Junko

AU - Sorensen, Erik J.

N1 - Funding Information: We thank The Skaggs Institute for Chemical Biology at TSRI, a Graduate Research Fellowship to J. T. (Abbott Laboratories), a Beckman Young Investigator Award to E. J. S., and a grant from the Merck Research Laboratories for their generous support of this research. We thank Professor Larry Overman and Dr. Adam Tomasi for samples of natural and synthetic (−)-hispidospermidin and helpful discussions. We also thank Professor Robin Polt for bringing the pioneering studies of A. McKenzie to our attention.

PY - 2003/8/25

Y1 - 2003/8/25

N2 - A concise, enantiospecific synthesis of the phospholipase C inhibitor (-)-hispidospermidin (1) has been achieved by approximating the architecture of a reactive intermediate that may lie on the biosynthetic pathway leading to this natural product. Two compounds derived from (R)-(+)-pulegone were joined by a highly diastereoselective carbonyl addition. A proximity-facilitated, acid-induced bicyclization of spiro[4.5]deca-1,7-diene 29 gave rise to the tetracyclic framework of 1 and was the key transformation in this synthesis.

AB - A concise, enantiospecific synthesis of the phospholipase C inhibitor (-)-hispidospermidin (1) has been achieved by approximating the architecture of a reactive intermediate that may lie on the biosynthetic pathway leading to this natural product. Two compounds derived from (R)-(+)-pulegone were joined by a highly diastereoselective carbonyl addition. A proximity-facilitated, acid-induced bicyclization of spiro[4.5]deca-1,7-diene 29 gave rise to the tetracyclic framework of 1 and was the key transformation in this synthesis.

KW - Biomimetic synthesis

KW - Hispidospermidin

KW - Proximity

KW - π-cyclization

UR - https://www.scopus.com/pages/publications/0041657471

UR - https://www.scopus.com/inward/citedby.url?scp=0041657471&partnerID=8YFLogxK

U2 - 10.1016/S0040-4020(03)00936-0

DO - 10.1016/S0040-4020(03)00936-0

M3 - Article

AN - SCOPUS:0041657471

SN - 0040-4020

VL - 59

SP - 6921

EP - 6932

JO - Tetrahedron

JF - Tetrahedron

IS - 35

ER -

A spontaneous bicyclization facilitates a synthesis of (-)-hispidospermidin

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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