Efficient and Practical Synthesis of the A-Ring Precursor of 19-nor-1α,25-Dihydroxyvitamin D₃ and Its ¹³C- or ²H-Labeled Derivative

Abstract

[reaction: see text] The A-ring precursor of 19-nor-1alpha,25-dihydroxyvitamin D(3) (1) and its (13)C- or (2)H-labeled derivative were efficiently synthesized from readily available, optically active 5-(tert-butyldimethylsilyloxy)-2-cyclohexenone (2) through a five-step reaction in 68% overall yield.

Simple, Efficient Chemoenzymatic Synthesis of (S)-5-(tert-Butyldimethylsilyloxy)-2-cyclohexenone and Enantiomeric Ketone Intermediates of 19-Nor-1α,25-dihydroxyvitamin D3

“…We planned to utilize this chiral intermediate 8 for the synthesis of ( S )-5-( tert -butyldimethylsilyloxy)-2-cylcopentenone ( 13) and both the enantiomeric forms of chiral ketone 7 (Scheme ). A recent report on the utility of 13 toward a vitamin D 3 analogue prompts us to report our findings.

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The Divalent Titanium Complex Ti(O-i-Pr)4/2i-PrMgX as an Efficient and Practical Reagent for Fine Chemical Synthesis

“…[69±71] Among them, the synthetic procedure for the A-ring precursor of 19-nor-1a,25-dihydroxyvitamin D 3 is shown in Equation 28. [71] Thus, epoxidation of the enone with aqueous H 2 O 2 / base and the following Wittig reaction with (EtO) 2 (O)PCH 2 CO 2 Et/NaH afforded the epoxy ester shown in Equation 28, from which the A-ring precursor was prepared by reductive epoxide ringopening with HCOOH/cat. Pd(0) and subsequent silylation of the hydroxy group.…”

Stereoselective construction of 3a-methylhydrindanes starting from 2,7-enynol derivatives based on Ti(II)-mediated cyclization and Ru-catalyzed ring-closing metathesis

“…As can be seen from Table 1 summarizing the results, all reactions predominantly produced the cyclized compound 3 with syn configuration regarding the methyl and R 2 groups. 6 Although the reaction of Z-2a having an OAc or OCO 2 Et moiety as a leaving group resulted in poor yield and/or low stereoselectivity (entries 2 and 4), high selectivity and good yield of syn-3a was attained by using 2a having OP(O)(OEt) 2 or Cl, irrespective of the olefin geometry of the starting 2a (entries [5][6][7][8]. Similarly, the reaction of enynes 2b-d having other alkyne substituents yielded the corresponding triene syn-3 selectively.…”