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. 2024 Feb 1;30(7):e202302996.
doi: 10.1002/chem.202302996. Epub 2023 Dec 11.

Enzymatic Resolution and Decarboxylative Functionalization of α-Sulfinyl Esters

Suraksha Gahalawat  1 , Yesu Addepalli  1 , Stephen P Fink  2 , Lakshmi Kasturi  3 , Sanford D Markowitz  4 , Joseph M Ready  1
Affiliations

Enzymatic Resolution and Decarboxylative Functionalization of α-Sulfinyl Esters

Suraksha Gahalawat et al. Chemistry. .

Abstract

α-Sulfinyl esters can be readily prepared through thiol substitution of α-bromo esters followed by oxidation to the sulfoxide. Enzymatic resolution with lipoprotein lipase provides both the unreacted esters and corresponding α-sulfinyl carboxylic acids in high yields and enantiomeric ratios. Subsequent decarboxylative halogenation, dihalogenation, trihalogenation and cross-coupling gives rise to functionalized sulfoxides. The method has been applied to the asymmetric synthesis of a potent inhibitor of 15-prostaglandin dehydrogenase.

Keywords: decarboxylation; halogenation; lipase; resolution; sulfoxides.

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Figures

Figure 1.
Figure 1.
Representative sulfoxide containing natural products and pharmaceutical agents.
Scheme 1.
Scheme 1.
Ester/acid interconversion allows access to both sulfoxide enantiomers.
Scheme 2.
Scheme 2.
Decarboxylative halogenation of α-sulfinyl carboxylic acids.
Scheme 3.
Scheme 3.
Synthesis of dihalosulfoxides. [a] Isolated yield over 2 steps.
Scheme 4.
Scheme 4.
Tribromination of α-sulfinyl acids.
Scheme 5.
Scheme 5.
Asymmetric synthesis of sulfoxide inhibitors of 15-prostaglandin dehydrogenase (15-PGDH).
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