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Syntheses nouvelles de la mevalonolactone marquee AU 14 C, 13 C, ‐ (RS) mevalonolactone ( 14 C 2 ‐4,5) et (RS) mevalonolactone ( 14 C‐5)
Author(s) -
Rousseau Bernard,
Beaucourt JeanPierre,
Pichat Louis
Publication year - 1983
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580200412
Subject(s) - chemistry , hydrochloric acid , ketone , hydrogen peroxide , yield (engineering) , alcohol , medicinal chemistry , stereochemistry , organic chemistry , metallurgy , materials science
Three new routes to (RS) mevalonolactone suitable for the double labeling with isotopic carbon at positions 4 and 5 or labeling at C‐5 are outlined. 1–(2,4.10‐trioxaadamantyl) propanone : 2 was prepared from 2‐(2.4, 10‐trioxaadamantul) acetylchloride 1 and bis‐(trimethylsilul) malonate. Addition of [ 14 C 2 ]‐ethinyllithium on 2 provided an 80 % yield of acetylenic alcohol : 3 . The latter was submitted to the regioselective gem terminal bishydroboration with 9‐BBN followed by oxidation with hydrogen peroxide and base leading to the 1,3‐diol : 5 , the hudrolysis of which, without isolation gave [4,5 14 C 2 ] mevalonolactone : 48 % overall yield based on Ba 14 CO 3 specific activity 98.5 mCi/mM. A second route following the same pattern started from commercial 1,1 dimethoxy 3‐butanone : 6 . Addition of [ 14 C 2 ] ethinyllithium with 6 gave the alcohol 7 which was treated with 9‐BBN followed by oxidation with hydrogen peroxide and base leading to the 1,3‐diol 8 which after chromatography was oxidized with bromine water in hydrochloric acid provided [4,5 14 C 2 ] mevalonolactone. This route was followed to provide 10 gm batches of [4,5‐ 13 C 2 ] mevalonolactone. The third scheme involved the condensation of ethyl lithio [1‐ 14 C] acetate with ketone : 2 followed by reduction with LiAlH4 of the resulting β‐ hydroxy‐ester 9 into 1, 3 diol : 10 which by hydrochloric hydrolysis gave rise to [5‐ 14 C] mevalonolactone : 50 % overall yield based on ethul acetate : specific activity : 50 mCi/mMole.