Improved and scalable synthetic route to the synthon 17-β-(2- Carboxyethyl)-1,3,5(10)-estratriene: An important intermediate in the synthesis of bone-targeting estrogens

Shama Nasim, Ashish P. Vartak, William M. Pierce, K. Grant Taylor, Peter A. Crooks

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

An improved, highly scalable methodology for the multigram-scale preparation of an important synthon, 17-β-(2-carboxyethyl)-1,3,5(10)- estratriene, is described. Previous approaches have failed to provide useful quantities of the analytically pure product because of facile retro-Michael breakdown of the-alkoxy carbonyl precursors during workup and isolation operations. The synthetic approach described herein has been designed specifically to sidestep this problematic breakdown process. This new scalable method of preparation overcomes a major hurdle in the exploration of structure-activity relationships centered around novel estradiol derivatives with bone-targeting properties and also provides a scalable process for subsequent developmental work.

Original languageEnglish (US)
Pages (from-to)772-781
Number of pages10
JournalSynthetic Communications
Volume40
Issue number5
DOIs
StatePublished - Jan 2010

Bibliographical note

Funding Information:
Financial support from Pradama, Inc. and the Kentucky Science and Technology Corporation is gratefully acknowledged. W.M.P., K.G.T., and P.A.C. have a financial interest in Pradama Inc.

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • Bone-targeting
  • Estradiol
  • Retro-Michael addition

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