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Approach to the Synthesis of Chlorothricolide: Synthesis of (±)-19,20-Dihydro-24-O-methylchlorotricolide, methyl ester, ethyl carbonate

Citation

Varney, Michael David (1986) Approach to the Synthesis of Chlorothricolide: Synthesis of (±)-19,20-Dihydro-24-O-methylchlorotricolide, methyl ester, ethyl carbonate. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/h9ke-rp15. https://resolver.caltech.edu/CaltechTHESIS:02272019-121930852

Abstract

An approach to the total synthesis of the 14-membered macrolide antibiotic aglycon chlorothricolide is presented. Key steps from the two halves to (±)-19,20-Dihydro-24-O methylchlorothricolide, methyl ester, ethyl carbonate include initial esterification across the C1 and C25 carbons followed by macrodilactonization across the C17 and C14 carbons. Ester enolate Claisen rearrangement and subsequent decarboxylation afforded the intact lactone. Functionalization of the top half is explored.

The ester enolate Claisen rearrangement of propionate derivatives of resolved 1-(t-butyldimethylsilyl)-trans-2-butene-1-ol is reported. Subsequent protiodesilation of the reduced and protected Claisen products resulted in the formation of 2,3-dimethyl-4-pentenyl ethers. Thus, the secondary α-silyl alcohol has functioned as a chiral primary alcohol equivalent.

The Claisen rearrangement of vinyl ethyl derivatives of 5-tert-butyl-1-(hydroxymethyl)-1-cyclohexene is reported. The standard allyl vinyl ether conditions as well as the triethyl orthoacetate and ester enolate variants of the Claisen rearrangement all resulted in the formation of cis(axial)-4-tert-butylcyclohexyl-substituted systems. Thus, in sterically unbiased cases, this [3.3] sigmatropic process results in the axial attachment of the side chain in a cyclohexyl system.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Ireland, Robert E.
Thesis Committee:
  • Dervan, Peter B. (chair)
  • Ireland, Robert E.
  • Grubbs, Robert H.
  • Goddard, William A., III
Defense Date:2 August 1985
Funders:
Funding AgencyGrant Number
Atlantic Richfield FoundationUNSPECIFIED
CaltechUNSPECIFIED
Record Number:CaltechTHESIS:02272019-121930852
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:02272019-121930852
DOI:10.7907/h9ke-rp15
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/ja00324a043DOIArticle adapted for Chapter 2.
https://doi.org/10.1021/jo00159a008DOIArticle adapted for Chapter 3.
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11412
Collection:CaltechTHESIS
Deposited By: Lisa Fischelis
Deposited On:28 Feb 2019 18:56
Last Modified:16 Apr 2021 22:12

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