Synthesis of 24-oxavitamin D3 and 1α-hydroxy-24-oxavitamin D3

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

“…Figure 6 (1993-1994) [118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136]. Compounds 225 [93] and 208 [108] were independently developed by different research groups and are important analogs functionalized at C-18 and C-11, respectively.…”

Efficient and scalable total synthesis of calcitroic acid and its 13C-labeled derivative

“…Starting from the commercially available Inhoffen-Lythgoe diol 2 we rst transformed the primary alcohol into a tosylate 9,10 followed by protecting the secondary hydroxyl group in the 7position as a tert-butyldimethylsilyl ether 8 3 (Scheme 2). Next, by a simple nucleophilic substitution reaction with cyanide the C1homologated nitrile 4 was prepared, 10,11 while by using 13 Clabeled NaCN the corresponding 13 C-labeled derivative 5 in position C23 (based on steroidal numbering) as obtained. The overall yield for these three reactions was 74%, independent whether 13 CN was used or not.…”

“…Therefore, the nitrile 4 was reduced by DIBAL to form the aldehyde. 10,11 It is important to do the hydrolysis of the aluminum/imine intermediate long enough otherwise the yield drops dramatically. Oxidation of the aldehyde was accomplished by the method of Pinnick and Lindgren 15 in quantitative yield and the carboxylic acid was directly transformed into the methyl ester 6 by using TMS-diazomethane in methanol.…”

Pd(0)‐Catalyzed‐Mediated Synthesis of Vitamin D Compounds

“…[43,[120][121][122] The Dienyne strategy J has been successfully applied to the synthesis of several vitamin D metabolites and analogs. [43,111,112,116,[123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141] This synthetic route has the following advantages: (1) the easy and short preparation of the A-ring-enyne synthons (bottom fragment); and (2) the easy preparation of the enol triflates (upper fragment) from the corresponding ketones. The main disadvantages are: (1) the overhydrogenation during Lindlar partial hydrogenation of the triple bond; (2) the low yield on vitamin D when thermal isomerization favors the previtamin D intermediate (for example 6-methyl-1,25D 3 analogs, [44] and aromatic-D-ring-1,25D 3 analogs; [45,46] and (3) the instability of the vitamin D compound under the thermal isomerization of the previtamin D form.…”

“…The Dienyne strategy J has been successfully applied to the synthesis of several vitamin D metabolites and analogs [43,111,112,116,123–141] . This synthetic route has the following advantages: (1) the easy and short preparation of the A‐ring‐enyne synthons (bottom fragment); and (2) the easy preparation of the enol triflates (upper fragment) from the corresponding ketones.…”