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Revision of previous work shows that PLE-cataiyzed hydrolysis of 1 leads to the (S)-alcohol 5 and not the (R)-alcohol 3 . However the homologue 2 gives the (R)-alcohol 4 .

The synthesis includes the side-chain construction starting from the Inhoffen-Lythgoe diol and coupling with the A ring. Both 23-oxa- and 23-thia-analogues showed a decreased cell differentiating effect but even a more decreased calcemic effect compared with 1α,25-(OH) 2 D 3 .

(1R,2S,3R,4S)-4-Butyryloxy-2,3-isopropylidenedioxy-cyclohexen-5-en-1-ol (1) is the common chiral building block for the 8 title pseudosugars. The hydroxymethyl substituent is introduced either via a radical reaction or via 2,3-Wittig rearrangement.

Disconnection at C20-C21 leads to two fragments. The C21-C27 fragment is constructed from D-isobutyl lactate via chelation-controlled allylation. The C17-C20 fragment is obtained from D-pantolactone.

Starting from erythritol, enzyme catalyzed construction of C4 chiral building blocks is described. The four diastereomeric protected tetroses are available from this single compound. Also an approach to L- and D-hexose-derivatives is presented.

A short and practical synthesis of the 1,7-enyne A-ring intermediate and of Uskokovic's phosphine-oxide precursor is described starting from the aldol product of acrolein with t-butyl acetate. Enantiopure β-hydroxy ester is obtained upon lipase-catalyzed resolution.

19-Nor-1 α,25-dihydroxyvitamin D 3 ( 2 ) was synthesized from A-ring precursor 5 and ketone 4 . Two synthesis of 5 were studied; one starting from (-)-quinic acid as a template and one starting from cis-1,3,5-cyclohexanetriol via a chemoenzymatic approach.

A convergent, more practical route to the A-ring precursors 3 and 5 starting from enantiopure (2S,4S)-1,2:4,5-diepoxypentane ( 11 ) is described.

14,20-Bis-epi-1α,25-dihydroxy-19-norvitamin D3 and side chain analogues thereof have been synthesised via the 14,20-bis-epi-Inhoffen–Lythgoe diol 9. The synthesis of this precursor was performed via degradation of vitamin D2 and by total synthesis starting from Hajos–Wiechert ketone 24.

The discovery that 1α,25-dihydroxyvitamin D3 is effective in the inhibition of cellular proliferation and in the induction of cellular differentiation has led to a search for analogues in which these activities and the classical calcemic activity of this hormone are separated. In this context, the synthesis and biological evaluation are reported of the three stereoisomeric CD-ring modified structural analogues in order to enforce a particular and different orientation of the 25-hydroxylated side chain. Comparison of the results of the biological evaluation and conformational analysis of the side chain suggests one defined and “active” geometry.

The synthesis and biological activities of seco C-9,11,21-trisnor-17-methyl-1 alpha,25-dihydroxyvitamin D(3) analogues (D-ring analogues) are described.

The synthesis and biological activity of novel CD-ring modified analogues of 22-oxa-1α,25-dihydroxyvitamin D3, lacking the D-ring and featuring a connection between C-12 and C-21 (cis-perhydrindane CE-ring analogues), is described. The synthesis of the CE-ring system follows Meyers' methodology for the preparation of enantiomerically pure hydrinden-2-ones. The analogues show a complete lack of binding affinity for the vitamin D receptor (pig nVDR) and of antiproliferative activity (MCF-7 cells), as compared to calcitriol.

Enantiomerically pure mono acylated derivatives of cis , cis -3,5-dihydroxy-1-(methoxycarbonyl)cyclohexane 1 , all- cis -3,5-dihydroxy-4-methyl-1-(methoxycarbonyl)cyclohexane 2 and all- cis -3,5-dihydroxy-4-ethyl-1-(methoxycarbonyl)cyclohexane 3 were obtained upon lipase catalyzed asymmetrization. PPL-catalyzed transesterification of 1 with vinyl acetate led in high yield to the ( S )-monoacetate (+)- 13 . With substrates 2 and 3 this process was slower and gave the ( R )-monoacetates (−)- 14 and (−)- 15 ; the best results were obtained with SAM II lipase. On the other hand, enantiotoposelective hydrolysis of their diacetates and especially dibutyrates gave useful results only for the 4-substituted substrates and produced the ( S )-monoesters.

A practical synthesis of trans-hydrindanone 5a from (+)-Wieland−Miescher ketone 8 is described. The target molecule 5a is a suitable precursor for the synthesis of analogues of 1α,25-dihydroxyvitamin D3 modified at C-16, C-17 or C-20. During the total synthesis it was found that hydroboration of (1,1)-ethylenedioxy-8a-methyl-1,2,3,4,6,7,8,8a-octahydronaphthalene (11) leads to a cis-decalin 13 instead of the literature reported trans-fusion.

An eleven-step, high-yielding (46%) synthesis of 1α-hydroxyvitamin D5 (2) starting from vitamin D2 (4) is described, in which a Julia olefination sequence is used for the construction of the (24R)-ethyl-substituted side chain.