Regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-L-ascorbic acid

John Prybylski; Nikki A. Thiele; Kenneth B. Sloan

doi:10.1016/j.tetlet.2016.02.112

Regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-L-ascorbic acid

John Prybylski, Nikki A. Thiele, Kenneth B. Sloan

Chemical Separations Group

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

An efficient regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of vitamin C 5,6-acetonide has been developed which does not involve tedious column chromatographic separation of the desired products from contaminants exhibiting very similar R_f values. Vitamin C 5,6-acetonide is first acylated with one equivalent of acyl halide in the presence of two equivalents of pyridine. The crude 2-O-acylated product is then alkylated with one equivalent of 1-acyloxyalkyl-1-iodide in the presence of one equivalent of triethylamine. The 2-O-acyl-3-O-(1-acyloxyalkyl) vitamin C 5,6-acetonides are obtained in moderate yields.

Original language	English
Pages (from-to)	1619-1621
Number of pages	3
Journal	Tetrahedron Letters
Volume	57
Issue number	14
DOIs	https://doi.org/10.1016/j.tetlet.2016.02.112
State	Published - Apr 6 2016

Keywords

Acylation
Alkylation
Prodrugs
Regioselective
Soft alkyl drug
Vitamin C

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10.1016/j.tetlet.2016.02.112

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title = "Regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-L-ascorbic acid",

abstract = "An efficient regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of vitamin C 5,6-acetonide has been developed which does not involve tedious column chromatographic separation of the desired products from contaminants exhibiting very similar Rf values. Vitamin C 5,6-acetonide is first acylated with one equivalent of acyl halide in the presence of two equivalents of pyridine. The crude 2-O-acylated product is then alkylated with one equivalent of 1-acyloxyalkyl-1-iodide in the presence of one equivalent of triethylamine. The 2-O-acyl-3-O-(1-acyloxyalkyl) vitamin C 5,6-acetonides are obtained in moderate yields.",

keywords = "Acylation, Alkylation, Prodrugs, Regioselective, Soft alkyl drug, Vitamin C",

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AU - Prybylski, John

AU - Thiele, Nikki A.

AU - Sloan, Kenneth B.

PY - 2016/4/6

Y1 - 2016/4/6

N2 - An efficient regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of vitamin C 5,6-acetonide has been developed which does not involve tedious column chromatographic separation of the desired products from contaminants exhibiting very similar Rf values. Vitamin C 5,6-acetonide is first acylated with one equivalent of acyl halide in the presence of two equivalents of pyridine. The crude 2-O-acylated product is then alkylated with one equivalent of 1-acyloxyalkyl-1-iodide in the presence of one equivalent of triethylamine. The 2-O-acyl-3-O-(1-acyloxyalkyl) vitamin C 5,6-acetonides are obtained in moderate yields.

AB - An efficient regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of vitamin C 5,6-acetonide has been developed which does not involve tedious column chromatographic separation of the desired products from contaminants exhibiting very similar Rf values. Vitamin C 5,6-acetonide is first acylated with one equivalent of acyl halide in the presence of two equivalents of pyridine. The crude 2-O-acylated product is then alkylated with one equivalent of 1-acyloxyalkyl-1-iodide in the presence of one equivalent of triethylamine. The 2-O-acyl-3-O-(1-acyloxyalkyl) vitamin C 5,6-acetonides are obtained in moderate yields.

KW - Acylation

KW - Alkylation

KW - Prodrugs

KW - Regioselective

KW - Soft alkyl drug

KW - Vitamin C

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DO - 10.1016/j.tetlet.2016.02.112

M3 - Article

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SN - 0040-4039

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IS - 14

ER -

Regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-L-ascorbic acid

Abstract

Keywords

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