Bernard Michael Hennessy

Stereoselective total synthesis of 1α,25S,26-trihydroxycholecalciferol

A total synthesis of 1α,25S,26-trihydroxycholecalciferol (2) has been accomplished via an efficient convergent approach. The remote chiral center at C-25 was introduced by a regiospecific and diastereoselective 1,3-dipolar cycloaddition of the C-23 nitrone 27 with methyl methacrylate. Subsequent transformation of the resulting isoxazolidine led to the key synthon 3, which on coupling to the anion 4 and deprotection produced the metabolite 2.

Stereospecific synthesis of the lythgoe's ring a aldehyde for the preparation of 1α-hdroxylated tachysterols and calciferols

Abstract The dihydroxyaldehyde 1 , an important intermediate for the synthesis of 1α-hydroxylated vitamin D derivatives via the corresponding tachysterol precursors, was prepared from (S)-(+)-carvone ( 6 ). The sequence involves as central step, the decarboxylation and rearrangement of the epoxyglycidic acid 15 , prepared from carvone oxide 7 .

Potent, selective MCH-1 receptor antagonists.

This paper describes the lead optimization of a new series of potent, selective, orally bioavailable, brain-penetrant MCH-1 receptor antagonists. A major focus of the work was to achieve a selectivity profile appropriate for in vivo efficacy studies and safety.

Total synthesis of 25-hydroxy-16,23E-diene vitamin D3 and 1α,25-dihydroxy-16,23E-diene vitamin D3: Separation of genomic and nongenomic vitamin D activities

Separation of genomic and nongenomic vitamin D activities was achieved by structural modification of 1,25-dihydroxy vitamin D3 by introduction of 16 and 23E double bonds. The modified compound 3, lacking a 1 alpha-hydroxy group, exhibits only nongenomic activity. Its 1 alpha-hydroxy relative 4 expresses fully both genomic and non-genomic activities. A total synthesis of analogues 3 and 4 is described.

Dipolar Cycloaddition Route to the Synthesis of 1a,25-Dihydroxy-26-norvitamin D2 Derivatives

The intramolecular dipolar cycloadditions of nitrones derived from aldehydes (8) and (14) were found to proceed with a high degree of diastereoselectivity. By taking advantage of the functionality and stereochemical features residing in the cycloadducts (10) and (11), respectively, the two novel vitamin D 2 derivatives (1c) and (1d) were synthesized

Total synthesis of 1α,25,28-trihydroxyergocalciferol

Abstract A convergent total synthesis of 1α,25,28-trihydroxyergocalciferol (1), using an available A ring synthon and a CD synthon which was prepared via a thermodynamically controlled dipolar cycloaddition of methyl 3,3-dimethylacrylate and a C-23 nitrone followed by subsequent removal of the nitrogen function, is described.