Stereochemistry at C-1 of geranyl pyrophosphate and neryl pyrophosphate in the cyclization to (+)- and (-)-bornyl pyrophosphate.

R Croteau,N M Felton,C J Wheeler

doi:10.1016/s0021-9258(18)88922-0

Abstract

(1R)-1-3H-labeled and (1S)-1-3H-labeled geranyl pyrophosphate and neryl pyrophosphate were prepared from the corresponding 1-3H-labeled aldehydes by a combination of enzymatic and synthetic procedures. Following admixture with the corresponding 2-14C-labeled internal standard, each substrate was converted to (+)-bornyl pyrophosphate and (-)-bornyl pyrophosphate by cell-free enzyme preparations from sage (Salvia officinalis) and tansy (Tanacetum vulgare), respectively. Each pyrophosphate ester was hydrolyzed, and the resulting borneol was oxidized to camphor. The stereochemistry of labeling at C-3 of the derived ketone was determined by base-catalyzed exchange, taking advantage of the known selective exchange of the exo-alpha-protons. By comparison of such exchange rates to those of product generated from (1RS)-2-14C,1-3H2-labeled substrate, it was demonstrated that geranyl pyrophosphate was cyclized to bornyl pyrophosphate with net retention of configuration at C-1 of the acyclic precursor, whereas neryl pyrophosphate was cyclized to product with inversion of configuration at C-1. The observed stereochemistry is consistent with a reaction mechanism whereby geranyl pyrophosphate is first stereospecifically isomerized to linalyl pyrophosphate which, following rotation about C-2-C-3 to the cisoid conformer, cyclizes from the anti-endo configuration. Neryl pyrophosphate cyclizes either directly or via the linalyl intermediate without the attendant rotation.

Highlights

(1R)-l-3H-labeledand (1S)-l-3H-labeled geranyplyrophosphate and neryl pyrophosphate were prepared from the corresponding 1-’H-labeled aldehydes by a combination of enzymatic and synthetic procedures
(1RS)-2-’4C,1-3Hz-labelesudbstrate,itwas demonstrated that geranyl pyrophosphate was cyclized to bornyl pyrophosphate with net retention of configuration at C-1 of the acyclic precursor, whereas neryl pyrophosphate wascyclized to product withinversion of configuration at C- 1.The observed stereochemistry is consistent with a reaction mechanism whereby gerany1 pyrophosphate is first stereospecifically isomerized to linalyl pyrophosphawtehich, following rotation about C-2-C-3 to the cisoid conformer, cyclizes from the anti-endo configuration
It has long been recognized that geranyl pyrophosphate, the ubiquitous C, intermediate of isoprenoid metabolism, cannot be converted directly to cyclohexanoid monoterpenes because of the topological constraints imposed by the trans-C-2-C-3 double bond of the acyclic prenyl chain

Summary

Introduction

(1R)-l-3H-labeledand (1S)-l-3H-labeled geranyplyrophosphate and neryl pyrophosphate were prepared from the corresponding 1-’H-labeled aldehydes by a combination of enzymatic and synthetic procedures. (1R)- and (1S)-l-3H-labelegderanyl pyrophosphate and neryl pyrophosphate to both (+)- and (-)-bornyl pyrophosphate and the stereochemical location of 3H in each product by selective exchange of the exo-a-hydrogen of the derived camphor.

Results

Conclusion