Kato L. Perlman

1α,25-dihydroxy-19-nor-vitamin D3, a novel vitamin D-related compound with potential therapeutic activity

1α,25-Dihydroxy-19-nor-vitamin D3 has been synthesized via oxidative degradation of the 1α-hydroxycylcovitamin intermediate. Preliminary studies indicate that the new analog induces the differentiation of human leukemia HL-60 cells, with little or no calcemic activity.

Novel synthesis of 19-nor vitamin d compounds

A convergent synthesis of 19-nor-vitamin D compounds, specifically 19-nor-1α,25-dihydroxyvitamin D₃, is disclosed. The synthesis can also readily be utilized for preparing other 1α-hydroxylated 19-nor-vitamin D compounds. The key step in the synthesis is a suitable application of Lythgoes procedure i.e. a Horner-Wittig reaction of the lithium anion of a phosphine oxide with a Windaus Grundmann ketone to give, after any necessary deprotection, the desired 19-nor-vitamin D compound.

20-Oxopregnacalciferols: Vitamin D compounds that bind the progesterone receptor

Abstract 20-Oxopregnacaliferols and 19-nor-20-oxopregnacalciferol were prepared from calciferol 22-aldehydes by an oxygenation procedure.

Purification of human serum vitamin D-binding protein by 25-hydroxyvitamin D3-Sepharose chromatography

25-Hydroxyvitamin D3-Sepharose was prepared by coupling 25-hydroxyvitamin D3-3 beta-(1,2-epoxypropyl)-ether to thio-activated Sepharose CL-6B, forming a protease-resistant linkage between the sterol and the matrix. Vitamin D-binding protein from human plasma was obtained 85-92% pure after ligand affinity chromatography. Subsequent hydroxylapatite chromatography provided homogeneous protein. The purified vitamin D-binding protein was fully active in regard to 25-hydroxyvitamin D3 and actin binding capabilities.

1α-Hydroxy-19-nor-vitamin D C-22 aldehyde. A valuable intermediate in the synthesis of side chain modifed 1α,25-dihydroxy-19-nor-vitamin D3

Abstract A side chain homologated 1α,25-dihydroxy-19-nor-vitamin D 3 analog was prepared in a double convergent synthesis with 1α-hydroxy-19-nor-vitamin D C-22 aldehyde as a key intermediate.

Microbial production of vitamin B12 antimetabolites: II. 2-Amino-4-keto-3-methylpentanoic acids from bacillus cereus 439

Abstract 2-Amino-4-keto-3-methylpentanoic acids were isolated as a diastereomeric mixture from Bacillus cereus 439 fermentations and found to be vitamin B 12 antimetabolites in a bioassay system based on the vitamin B 12 -requiring Escherichia coli (Davis 113-3). A similar diastereomeric mixture with bioactivity was synthesized by condensation of 2-bromo-3-butanone with sodio diethyl acetamidomalonate followed by hydrolysis with 6 N HCl and purification by ion-exchange chromatography. The growth inhibitory effects of the antimetabolite were reversed by vitamin B 12 , l -methionine, l -isoleucine, l -leucine, l -valine, and d -alanine.

Vitamin D C-22 aldehydes. New key intermediates for the synthesis of side chain modified vitamin D analogues

Abstract Vitamin D C-22 aldehyde and 1α-hydroxyvitamin D C-22 aldehyde were efficiently synthesized starting from the readily available 22,23-bisnorcholenic acid. The usefulness of the compounds as common intermediates for the synthesis of side chain modified analogues of vitamins D2 and D3 has been demonstrated.

A convenient synthesis of (24S)-1α-hydroxyvitamin D2

A new method was developed for the synthesis of (2R)- and (2S)-2,3-dimethylbutyl p-tolyl sulphone from a chiral sulphinate ester, and applied to the synthesis of (24S)-1α-hydroxyvitamin D2; this new 24-epimer of vitamin D2 has a distinct biological activity profile, differing qualitatively from that known for the (24S)-isomer.

A new tritium-release assay for 25-hydroxyvitamin D-1α-hydroxylase

A new, rapid assay for 1 alpha-hydroxylase has been developed using 25-hydroxy-[1 alpha-3H]vitamin D3 as the substrate. Using the solubilized and reconstituted chick 1 alpha-hydroxylase, conversion of this substrate to 1,25-dihydroxyvitamin D3 causes the release of tritium into the aqueous medium. This 3H2O can be easily separated from the labeled substrate by passing the reaction mixture through a reverse-phase silica cartridge. The release of tritium is stereospecific as evidenced by the lack of 3H2O formed when 25-hydroxy-[1 beta-3H]vitamin D3 is used as the substrate. In parallel reactions containing the 25-hydroxy-[26,27-3H]vitamin D3 substrate, production of labeled 1,25-dihydroxyvitamin D3 was assessed by extraction and high-performance liquid chromatography and found to agree very closely with the amount of 3H2O produced from 25-hydroxy-[1 alpha-3H]vitamin D3, validating the accuracy of the new assay. Finally, a major advantage of the tritium-release assay for 1 alpha-hydroxylase is that the results are not affected by further metabolism of the 1,25-dihydroxyvitamin D formed in the incubations.

Synthesis of novel 20-oxo-pregnacalciferol analogs with binding affinity to the progesterone receptor

Abstract 3-Desoxy-20-oxo-19-nor-pregnacaliferol (6a) and its 2-oxo analog 6c were prepared from 22-acetoxy-Grundmanns ketone 1 and the corresponding (cyclohexylidene)ethyl phosphine oxides 2a, b and their binding to the progesterone receptor examined.