Bufadienolides. 7. Synthesis of 3β-Acetoxy-5α,14α;-bufa-20,22-dienolide

George Pettit; Dyral C. Fessler; Kenneth D. Paull; Peter Hofer; John C. Knight

doi:10.1021/jo00830a031

Bufadienolides. 7. Synthesis of 3β-Acetoxy-5α,14α;-bufa-20,22-dienolide

George Pettit, Dyral C. Fessler, Kenneth D. Paull, Peter Hofer, John C. Knight

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Abstract

A new synthetic route to 5-substituted 2-pyrones is described. Alkylation of enamine 1 with methyl acrylate, cyclization of carboxylic acid 2b employing p-toluenesulfonic acid in benzene, and dehydrogenation of enol lactone 3 with a palladium catalyst or by a N-bromosuccinimide sequence comprised the key steps to a-pyrone S. Other methods (utilizing derivatives of acetic acid) investigated for the enol lactonization reaction gave mainly lactone 4. Application to bufadienolide chemistry was studied by transformation of dehydroepiandrosterone via intermediates 6-8 to 3β-acetoxy-14α-bufa-5,20 (21)-dienolide (9). Similar conversion of epiandrosterone acetate (10) led to bufenolide 16, which was dehydrogenated to bufadienolide 17 using sulfur. Other dehydrogenation methods, including those quite useful with enol lactone 3, were unsatisfactory.

Original language	English (US)
Pages (from-to)	1398-1404
Number of pages	7
Journal	Journal of Organic Chemistry
Volume	35
Issue number	5
DOIs	https://doi.org/10.1021/jo00830a031
State	Published - May 1 1970

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Organic Chemistry

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title = "Bufadienolides. 7. Synthesis of 3β-Acetoxy-5α,14α;-bufa-20,22-dienolide",

abstract = "A new synthetic route to 5-substituted 2-pyrones is described. Alkylation of enamine 1 with methyl acrylate, cyclization of carboxylic acid 2b employing p-toluenesulfonic acid in benzene, and dehydrogenation of enol lactone 3 with a palladium catalyst or by a N-bromosuccinimide sequence comprised the key steps to a-pyrone S. Other methods (utilizing derivatives of acetic acid) investigated for the enol lactonization reaction gave mainly lactone 4. Application to bufadienolide chemistry was studied by transformation of dehydroepiandrosterone via intermediates 6-8 to 3β-acetoxy-14α-bufa-5,20 (21)-dienolide (9). Similar conversion of epiandrosterone acetate (10) led to bufenolide 16, which was dehydrogenated to bufadienolide 17 using sulfur. Other dehydrogenation methods, including those quite useful with enol lactone 3, were unsatisfactory.",

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T1 - Bufadienolides. 7. Synthesis of 3β-Acetoxy-5α,14α;-bufa-20,22-dienolide

AU - Pettit, George

AU - Fessler, Dyral C.

AU - Paull, Kenneth D.

AU - Hofer, Peter

AU - Knight, John C.

PY - 1970/5/1

Y1 - 1970/5/1

N2 - A new synthetic route to 5-substituted 2-pyrones is described. Alkylation of enamine 1 with methyl acrylate, cyclization of carboxylic acid 2b employing p-toluenesulfonic acid in benzene, and dehydrogenation of enol lactone 3 with a palladium catalyst or by a N-bromosuccinimide sequence comprised the key steps to a-pyrone S. Other methods (utilizing derivatives of acetic acid) investigated for the enol lactonization reaction gave mainly lactone 4. Application to bufadienolide chemistry was studied by transformation of dehydroepiandrosterone via intermediates 6-8 to 3β-acetoxy-14α-bufa-5,20 (21)-dienolide (9). Similar conversion of epiandrosterone acetate (10) led to bufenolide 16, which was dehydrogenated to bufadienolide 17 using sulfur. Other dehydrogenation methods, including those quite useful with enol lactone 3, were unsatisfactory.

AB - A new synthetic route to 5-substituted 2-pyrones is described. Alkylation of enamine 1 with methyl acrylate, cyclization of carboxylic acid 2b employing p-toluenesulfonic acid in benzene, and dehydrogenation of enol lactone 3 with a palladium catalyst or by a N-bromosuccinimide sequence comprised the key steps to a-pyrone S. Other methods (utilizing derivatives of acetic acid) investigated for the enol lactonization reaction gave mainly lactone 4. Application to bufadienolide chemistry was studied by transformation of dehydroepiandrosterone via intermediates 6-8 to 3β-acetoxy-14α-bufa-5,20 (21)-dienolide (9). Similar conversion of epiandrosterone acetate (10) led to bufenolide 16, which was dehydrogenated to bufadienolide 17 using sulfur. Other dehydrogenation methods, including those quite useful with enol lactone 3, were unsatisfactory.

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Bufadienolides. 7. Synthesis of 3β-Acetoxy-5α,14α;-bufa-20,22-dienolide

Abstract

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