Efficient synthesis of 1alpha-fluoro A-ring phosphine oxide, a useful building block for vitamin D analogues, from (S)-carvone via a highly selective palladium-catalyzed isomerization of dieneoxide to dieneol

The 1alpha-fluoro A-ring phosphine oxide 1, a useful building block for fluorinated vitamin D analogues, was synthesized from (S)-carvone in 13 synthetic steps, and only five isolations, in 22% overall yield. In the key synthetic step, a highly selective palladium-catalyzed isomerization of dieneoxide 18 to dieneol 20 was achieved using an appropriately selected fluorinated alcohol as a catalytic proton source.     

Enantioselective synthesis of a potential key intermediate for the total synthesis of fumagillin

Key intermediate, 7, of a projected total synthesis of the anti-angiogenesis compound Fumagillin 1 and the semi-synthetic analogue TNP-470 2, has been prepared in enantiomerically pure form by employing an early nucleophilic addition ring closure [NARC] sequence to construct the cyclohexene backbone.     

Efficient synthesis of the A-ring phosphine oxide building block useful for 1 alpha,25-dihydroxy vitamin D(3) and analogues

The 1 alpha-hydroxy A-ring phosphine oxide 1, a useful building block for vitamin D analogues, was synthesized from (S)-carvone in nine synthetic operations and a single chromatographic purification in 25% overall yield. The synthesis features two novel efficient synthetic transformations: the Criegee rearrangement of alpha-methoxy hydroperoxyacetate 10 in methanol to obtain directly the desired secondary 3 beta-alcohol 11 and the highly chemo- and stereoselective isomerization of dieneoxide ester (E)-7 to the 1 alpha-allylic alcohol with an exocyclic double bond (E)-8. Further insight into the selectivity control of the latter rearrangement was obtained from the reactions of (Z)-epimeric substrates. The new synthetic approach leading to the 1 alpha-hydroxy epimers complements our previously reported synthesis of the corresponding 1 beta-epimers, thus producing all stereoisomers of these versatile building blocks efficiently from carvone.     

A novel stereoselective synthesis of a chiral key intermediate for the preparation of vitamin D3

The cyclopentanone 3a, a key intermediate in the synthesis of vitamin D₃ and its metabolites, has been prepared in optical active form using(S)-γ-trityloxymethyl-γ-butyrolactone (6) as a chiral building block.     

An enantioselective synthesis of the A-ring synthon for vitamin D3 metabolites by chemicoenzymatic approach

The A-ring synthon for vitamin D3 metabolites having 1α hydroxyl group is synthesized starting from a chiral monoester 6 enzymatically generated.     

Enantioselective route to a key intermediate in the total synthesis of forskolin

An enantioselective route for the total synthesis of forskolin, a potent activator of adenylate cyclase, has been developed which is based on reduction of dienone 3 to the (S)-alcohol 4 and conversion in two steps to tricyclic lactone 9, obtained in optically pure form simply by recrystallization.     

Enantioselective synthesis of a key intermediate of Levofloxacin using microbial resolution

The important key intermediate in the synthesis of Levofloxacin, (S)-7,8-difluoro-2,3-dihydro-3-methyl-4H-1,4-benzoxazine, was prepared enantioselectively by microbial resolution. When lyophilized microorganism selected from soil was treated with the corresponding amide, the (S)-amine was obtained with high enantiomeric purity (99% ee).     

Furan approach to the synthesis of the A-ring of Vitamin D analogues

The efficient transformation of 2,3-disubstituted furan (3) into (Z)-dienol (2) illustrates a useful strategy for the synthesis of the A-ring of Vitamin D analogues.     

Mevinic acids and analogues: preparation of a key chiral intermediate

The preparation of methyl 3-0-tert-butyldiphenylsilyl-2,4-dideoxy-β-$\text{D}$-$\text{erythro}$- hexopyranoside, a key chiral intermediate for mevinic acids, and its elaboration into four mevinate analogues are described.     

Hydroxylation of a vitamin D A-ring fragment

Summary When the benzoate of (S)-(Z)-2-(5-(tert-butyldimethylsiloxy)-2-methylencyclohexyliden)-ethanol (5) is treated with 2.5 equivalents of Hg(OOCCF₃)₂ in dryTHF, a smooth and selective allylic hydroxylation occurs. The C-1 functionalized vitamin D A-ring synthon6 is isolated in 65 to 70% yield in a single step.

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Hydroxylierung eines Vitamin D A-Ring-Fragments (Kurze Mitt.)

Zusammenfassung Umsetzung des Benzoats von (S)-(Z)-2-(5-(tert-Butyldimethylsiloxy)-2-methylencyclohexyliden)-ethanol (5) mit 2.5 Äquivalenten Hg(OOCCF₃)₂ in trockenemTHF führt zu einer selektiven allylischen Hydroxylierung. Damit ist das an C-1 funktionalisierte Vitamin D A-Ring-Fragment6 in einem einzigen Schritt in einer Ausbeute von 65 bis 70% zugänglich.

     

Enantioselective synthesis of an aziridinomitosane and selective functionalizations of a key intermediate

An enantioselective synthesis of mitosane core (-)-1 has been achieved. Key steps include a rapid assembly of a key eight-membered-ring intermediate employing ring-closing metathesis. Kinetic resolution of an advanced secondary alcohol was then accomplished by using a peptide-based asymmetric acyl transfer catalyst that was discovered from a parallel screen of catalyst candidates. Optically pure material was then converted to the mitosane core, which was the subject of additional studies on the selective modification to produce several substituted compounds containing a mitosane ring system.     

Vitamin D: a concise synthesis of the C19 hydroxylated enyne A-ring, an interesting precursor for the preparation of C19 substituted vitamin D analogues

A new C₁₉ hydroxylated enyne 15, as potential A-ring building block of vitamin D analogues, was synthesized in enantiomerically pure form in nine steps from (−)-(S)-limonene. This short synthesis involved ozonolyzis of 1,2-limonene oxide followed by a Criegee rearrangement, epoxide trans diaxial ring opening by lithium acetylide, elimination, epoxidation and syn β-elimination of the resulting homopropargylic oxirane.     

Continuous-flow synthesis of activated vitamin D3 and its analogues

An efficient, two-stage, continuous-flow synthesis of 1α,25-(OH)(2)-vitamin D(3) (activated vitamin D(3)) and its analogues was achieved. The developed method afforded the desired products in satisfactory yields using a high-intensity and economical light source, i.e., a high-pressure mercury lamp. In addition, our method required neither intermediate purification nor high-dilution conditions.     

光学活性Zoapatanol类似物的合成研究 - 关键中间体的合成

手性合成原2经格氏反应、甲基烯丙醇双阴离子环氧化合物开环等七步反应,合成了光学活性Zoapatanol类似物1b的关键中间体8. 化合物5a～8的新手性中心经证明为S构型。     

Synthesis of an optically active intermediate for A-ring of 19-nor- 1α,25-dihydroxyvitamin D3

An optically active intermediate 5 for A-ring of 19-nor-1a,25-dihydroxyvitamin D3 2 has been synthesized in five steps, starting from readily available, inexpensive D( )-xylose 6 with good yield.     

Facile synthesis of a key intermediate for the synthesis of prostanes and isoprostanes

An unconventional ring opening of β-sultines followed by an elimination step was achieved, leading to the formation of an important synthon for various prostanes and isoprostanes.