Approaches to the Synthesis of the Ophiobolin Ring System
Senter, Peter Dana
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https://hdl.handle.net/2142/70173
Description
Title
Approaches to the Synthesis of the Ophiobolin Ring System
Author(s)
Senter, Peter Dana
Issue Date
1981
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Abstract
The ophiobolin and ceroplastol sesterterpenes have been isolated from a variety of different insects and microorganisms. The unusual structures and biological activities of these compounds have prompted us to undertake studies directed towards their total synthesis. The synthetic plan involved the application of an intramolecular photocycloaddition reaction of (DELTA)('(alpha),(beta))-butenolide derivatives and the reductive cleavage of the derived cyclobutanes. This procedure provides a novel method for effecting two-carbon ring expansion.
(DELTA)('(alpha),(beta))-Butenolides were prepared from 2-bromocyclohexene derivatives by halogen-metal exchange and carboxylation with carbon dioxide. Thus, a series of butenolides with 3,4-pentadienyl, 3-butenyl, and 3-pentenyl sidechains in the (gamma)-position were prepared. Photolysis of butenolides with 3-butenyl and 3-pentenyl sidechains gave fused tetracyclic lactones in good yield. In contrast, photolysis of the butenolide with a 3,4-pentadienyl sidechain gave a mixture of fused and bridged photoadducts. Hydrolysis of the lactones and oxidation of the hydroxy acid salts with sodium ruthenate afforded tricyclic keto acids in good yield. Lithium in ammonia reduction gave cyclopentacyclooctene derivatives. These compounds correspond to the A and B rings of the ophiobolin and ceroplastol sesterterpenes. The overall transformation of cyclohexene derivatives to bicyclic cyclopentacyclooctenes constitutes an efficient annelative two-carbon ring expansion procedure.
The synthesis of the tricyclic ring system found in the natural products required multigram quantities of trans-octahydro-7a-methyl-5H-5-one which was prepared from the Wieland-Miescher ketone in eleven steps in 22% overall yield. Reaction with the bromo Vilsmeier reagent gave the corresponding bromo aldehyde. Addition of the Grignard reagents derived from 5-bromo-2-pentene and 4-bromo-1-butene afforded diastereomeric bromo alcohols which were purified by MPLC. The tricyclic (DELTA)('(alpha),(beta))-butenolides were prepared as before by metalation and carboxylation. The photolysis of the tricyclic lactones effected intramolecular {2 + 2} cycloaddition to form fused pentacyclic lactones in high yield. Reductive ring opening of the derived keto acids gave dicyclopenta{a,d}cyclooctene derivatives related to the ophiobolin and ceroplastol sesterterpenes.
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