Wisconsin Alumni Research Foundation

Tetrionics, Inc.

Herbert E Paaren

Hector Floyd Deluca

Heinrich K Schnoes

David E Hamer

Joseph K Wichmann

Mary A Fivizzani

Yoko Tanaka

Connie M Smith

Helen Frank

Steven R Duff

Synthesis of 2-hydroxyestradiol derivatives

This invention provides a novel synthesis and crystallization method and solvent for producing hexafluoro-vitamin D compounds, including 26, 26, 26, 27, 27, 27-hexafluoro-1.alpha., 25-dihydroxyvitamin D.sub.3. Crystalline forms of such compounds are provided that are especially suited for pharmaceutical use. Such compounds can exhibit biological activity for treating cancers, osteoporosis and psoriasis.

Hexafluoro-vitamin synthesis and crystallization method, solvent and

19-nor-vitamin D analog compounds and a method of synthesizing such compounds are disclosed. More particularly, examples of such compounds include 14-epi-19-nor-1.alpha.,25-dihydroxyvitamin D.sub.3, 14-epi-20-epi-19-nor-1.alpha., 25-dihydroxyvitamin D.sub.3, 14-epi-20-epi-19-nor-1.alpha.-hydroxyvitamin D.sub.3, 14-epi-19-nor-1.alpha., 25-dihydroxyvitamin D.sub.2, 14-epi-19-nor-24-homo-1.alpha., 25-didydroxyvitamin D.sub.3, 14-epi-19-nor-20(S)-hydroxymethyl-1.alpha.-hydropregnacalciferol, and 14-epi-19-nor-20(R)-hydroxymethyl-1.alpha.-hydroxypregnacalciferol.

14-EPI-19-nor-vitamin D compounds and methods

This invention is directed to a new class of vitamin D compounds which are characterized by a modified ring A and triene structures and to a method for preparing same. The 7,8-dihydroxy-, 10.19-dihydroxy- and 10-oxo-19-nor-analogs of 25-hydroxyvitamin D.sub.3 are specifically disclosed.

Ring A- and triene-modified vitamin D compounds

A process for preparing biologically active 1.alpha.-hydroxyvitamin D compounds from vitamin D compounds by hydroxylation at carbon 1 and subsequent photochemical isomerization, and novel intermediates and products resulting from this process are provided.

1-Hydroxylation process

The invention provides methods for preparing the various isomeric forms of 25-hydroxyvitamin D.sub.3 -26,23-lactone utilizing cyanohydrin formation with readily prepared steroid materials followed by actinic radiation of the products and recovery of the desired 25-hydroxyvitamin D.sub.3 -26,23-lactone. The invention also provides new intermediate compounds in their various isomeric forms derived during the process for preparing the said vitamin D.sub.3 lactones. 25-Hydroxyvitamin D.sub.3 -26,23-lactone is recognized as having vitamin D-like activity and is believed to play an important role in the regulation of calcium and phosphate levels in the animal and human organism. The present invention provides a convenient method for preparing the various isomeric forms of this compound.

Process for preparing vitamin D-lactones

The invention provides a method for chemically activating vitamin D compounds to obtain active rodenticidal preparations. The activated vitamin D preparation offers an effective and relatively inexpensive rodenticidal material.

Activated vitamin D rodenticides

The invention provides a new vitamin D compound, 1.alpha.,25-dihydroxy-vitamin D.sub.3 26,23-lactone. The compound is characterized by vitamin D-like activity.

Vitamin D-lactone derivative and process for preparing same

A method for isotopically labeling carbon-6 of vitamin D and 5,6-trans-vitamin D compounds which comprises reducing the corresponding 6-oxo-cyclovitamin with a tritio- or deutero-borohydride and subjecting the reduction product to acid-catalyzed solvolysis. The 6-labeled compounds find application in the elucidation of vitamin D metabolism and function and in vitamin metabolite analyses.

Vitamin D compounds isotopically substituted at carbon 6 and process for

A method for preparing 1.alpha.-hydroxylated vitamin D compounds from 5,6-trans-vitamin D compounds which comprises allylically oxidizing a 5,6-trans-vitamin D compound, subjecting the oxidation product to actinic radiation in the presence of a photosensitizing agent and recovering the 1.alpha.-hydroxylated compound. 1.alpha.-hydroxylation is recognized as being essential to impart biological activity to vitamin D compounds and their derivatives. The present invention provides an efficient method for maximizing the yield of 1.alpha.-hydroxylated vitamin D compounds.

Process for preparing 1-hydroxylated vitamin D compounds from

An improved method for the preparation of 1.alpha.-hydroxylated vitamin D compounds involving directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors or derivatives thereof, wherein the 1.alpha.-hydroxycyclovitamin D intermediate is solvolyzed directly, without first converting the 1-hydroxy group to a 1-O-acyl function as a protective measure.

Process for preparing 1.alpha.-hydroxylated compounds

A method for preparing 1.alpha.-hydroxyvitamin D compounds from 1.alpha.-hydroxy-3,5-cyclovitamin D compounds which comprises solvolyzing the 3,5-cyclovitamin D compound, exposing the solvolysis reaction products to actinic radiation in the presence of a photosensitizing agent and recovering the 1.alpha.-hydroxylated vitamin D compounds. 1.alpha.-hydroxylation is recognized as being essential to impart biological activity to vitamin D compounds and their derivatives. The present invention provides an efficient method for maximizing the yield of 1.alpha.-hydroxylated vitamin D compounds.

Process for preparing 1.alpha.-hydroxyvitamin D compounds from

A method for directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors of derivatives thereof which comprises subjecting such molecules to allylic oxidation utilizing selenium dioxide as the oxidizing agent.

A method for directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors or derivatives thereof which comprises subjecting such molecules to allylic oxidation utilizing selenium dioxide as the oxidizing agent.

Growing community of inventors

Verona, WI, United States of America

Herbert E Paaren