0.39 mmol) and lithium borohydride (0.2 mL of a 2 M solution in tetrahydrofuran, 0.4 mmol) in 1.8 mL of tetrahydrofuran was stirred for 1.5 h at -78 O C . The reaction was quenched with acetic acid and methanol; the mixture was then allowed to warm to room temperature. The volatiles were removed in vacuo, and the residue was separated by two successive stages of TLC: the first plate was developed with acetone/chloroform (3:2) to remove unreacted 5; the second plate was developed with chloroform/methanol(91) to yield 40 mg (40%) of l l d and 21 mg (21%) of 10d, which exhibited spectrometric properties indistinguishable from those previously reported.'s (b) 1Od by Desilylation of loa. To a cooled (ice bath) solution of 10a (114 mg, 0.28 mmol) in 25 mL of tetrahydrofuran was added 0.28 mL of a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran. The reaction was complete (TLC) in 30 min. The volatiles were removed, and the resulting residue was purified by preparative TLC using acetone/chloroform (3:2) (R, 0.26) for development to yield 67 mg (94%) of 10d.(c) 1 Id by Desilylation of 1 la. Desilylation of 1 la (125 mg, 0.30 "01) was accomplished according to the procedure described above for desilylation of 10a to afford 66 mg (86%) of Ild: R, 0.49 (9:l chloroform/methanol); MS, m / z (relative intensity) 257 la,25Dihydroxycholecalciferol(4) and la,25-dihydroxyergocalciferol(7), the hormonally active forms of vitamin
D3(1) and vitamin D2 (5), were synthesized by a Horner-Wittig reaction of the phosphine oxide 11 with the ketones 10 and 12, respectively. The synthon 11 was obtained by a sequence that involves the stereospecific opening of epoxide 15, with sodium acetate in acetic acid, followed by oxidative degradation of the isopropenyl side chain and dehydration of the intermediate 22. Photoisomerization of the resulting 23 gave 24, which was finally converted to 11. The hydroxylated ketone 10 was obtained from the known intermediate 28. The introduction of the 25-hydroxy side chain was achieved by reaction of the lithium derivative of 30 with the tosylate 29 to give 31, which was catalytically hydrogenated to 32 and then converted to 10. The ketone 12 was prepared by a stereocontrolled route that involves as the key step, the [3 + 21 dipolar cycloaddition of nitrone 35 with methyl 3,3-dimethylacrylate (36) to give a 1:l mixture of isoxazolidines 37 and 38. Stereochemical control was achieved by taking advantage of the thermal reversibility of the cycloaddition, which allows the reequilibration of undesired 37. Isoxazolidine 38 was readily transformed to 43 by reduction, followed by elimination of the nitrogen function, and finally oxidation to 12.In the past two decades, extensive investigations of the vitamin D, (cholecalciferol, 1) metabolism have led to the discovery of a number of transformations which this essential vitamin undergoes in biological systems.2 The most fundamental of these transformations is the sequence of hydroxylations of 1, which starts in the liver to give 25hydroxycholecalciferol...
