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The first synthesis of 1α,25-dihydroxy-3-epi-vitamin D2 is described. Key steps of the synthesis entail the construction of the triene unit by a Pd-catalyzed ring closure of an enol-triflate (A-ring fragment) followed by a Suzuki–Miyaura coupling with a boronate (upper fragment), and the installation of the methyl group at C-24 by an SN2′-syn displacement of an allylic carbamate. This article is part of a Special Issue entitled ‘SI:17th Vitamin D Workshop’.

A short, flexible approach to 25-functionalized vitamin D3 analogues including 26,27-hexadeutero-25 hydroxyvitamin D3 is described.

Coupling of the CD fragment, ketone 6 (obtained by partial synthesis from vitamin D2), either directly (Horner-Wittig route) or via the derived enol triflate (dienyne route) with the appropriate A-ring fragment, phosphine oxide anion 7 or enyne 10, is the key step in the syntheses of 24-oxavitamin D3 (1d) and 1α-hydroxy-24-oxavitamin D3 (1e), respectively. © 1993.

A versatile method for the rapid construction of fragments related to the upper part of vitamin D3 from the Lythgoe-Inhoffen diol is described. The key feature of the strategy is a new zinc-copperinduced conjugate addition of iodo triflate 10a to electron-deficient olefins under sonochemical aqueous conditions. These fragments are rapidly and efficiently transformed via the dienyne convergent approach to several derivatives of the hormone 1α,25-(OH)2-D3 modified at C-25. © 1993, American Chemical Society. All rights reserved.

The application of Negishi's cyclization methodology to the synthesis of (Z)-1-iodo-1,3- bis -exocyclic-dienes from acyclic precursors is described. This kind of compounds can be used for the preparation of conjugated systems such us the triene of vitamin D.

An efficient convergent synthesis of the iodide 6a , which contains the vitamin D triene system, and the ultrasonically induced reactions between 6a and 6b and electron-deficient olefins to give several vitamin D 3 analogues with modified side chains are described.

Temporary connection of alkenes to 3-alkoxy-4-pyrones via sulfur or silicon tethers allows their thermal [5 + 2] cycloaddition and ensures complete regio- and stereochemical control. © 1993, American Chemical Society. All rights reserved.

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.

3-Hydroxy-4-pyridones, which are easily prepared from commercially available 3-hydroxy-4-pyrones, can be readily transformed into 4-methoxy-3-oxidopyridinium ylides by treatment with methyl trifluoromethanesulfonate and subsequent deprotonation with a non-nucleophilic base. These ylides are capable of undergoing cycloaddition to several electron-deficient alkenes, thus allowing the synthesis of highly functionalized azabicyclo[3.2.1]octane moieties. The rich substitution patterns of these frameworks might allow their divergent conversion to a variety of natural and non-natural tropane alkaloids.

An efficient, versatile synthesis of Lythgoe-Phosphine Oxide has been developed starting from l-carvone. The key steps are rupture of protected epoxide 7 to give dicarbonyl compound 8, preparation of vinylic triflate 2, and palladium-catalysed cyclization-carbonylation of vinylic triflate 2.

1 α ,24( R )-Dihydroxyvitamin D 3 ( 5e ) was synthesized. The key step in the preparation of the side-chain was opening of the chiral epoxide 10 by the α-anion of the nitrile 9 . The triene system was synthesized by the dienyne route.

This work describes our studies on the functionalization at C11 of CD-ring fragments of vitamin D3 using organocopper reagents. As an application, an efficient, convergent synthesis of 11α-[3,3-(dimethoxy)propyl] calcitriol analogue 2, which may be useful for the construction of affinity columns for the purification of 1α,25-(OH)2-vitamin D3 receptors, is described.

A series of semi-rigid analogues of the hormone 1α,25-dihydroxyvitamin D3 have been designed in order to study the topology required for binding to the hormone receptor (VDR). The new vitamin D3 analogues 2-5 possess a rigid C17-C20 bond and minimal structural modifications on the side-chain with respect to the hormone. Key steps for the introduction of the side-chains of the new analogues 2-5 from hydrindanone 6 involve a stereoselective Wittig reaction, olefin isomerization and dihalocyclopropanation.

Efficient preparation of two vitamin D CD ring system synthons with pyrazole rings in their side chains is based on the formation of the pyrazole ring from an α-acetylenic ketone.

A short and efficient synthesis of the 25-hydroxy Windaus-Grundmann ketone from the Inhoffen-Lythgoe diol is described (seven steps, 70% overall). The most relevant feature of the synthesis is the preparation of the Wittig reagent 3 from cheap and commercially available starting materials. Pure 3 can be obtained in multigram quantities for achieving clean and efficient Wittig reactions. (C) 2000 Elsevier Science Ltd.

The synthesis of a new class of vitamin D analogues having a cyclic side chain is described. Readily available starting material, a short sequence with high yielding steps are key features of the synthesis. Alcohols 12c and 12d were readily separable by flash chromatography and the stereochemistry at C22 was established unambiguously by X-ray diffraction analysis of 12c .

Although considerable efforts have gone into the stereocontrolled synthesis of side chains of important steroids with the “natural” chirality at C-20, little has been done on the stereocontrolled introduction of the “unnatural” chirality present in unusual marine steroids.1 Recently, we reported for the first time that steroidal α-face (2,3)-sigmatropic rearrangements of alkoxy-organolithium reagents provide an efficient method for the stereospecific introduction of the “natural” chirality at C-20.2a We now describe how this method can be applied to the stereospecific construction of the “unnatural” chirality at C-20 through the more hindered β-face.

We describe the reaction of new organocuprates of the form ArRTCuLi (Ar an ortho-heterosubstituted non-transferable ligand), and their reactions with simple α,β-unsaturated ketones.