Syntheses nouvelles de la mevalonolactone marquee AU ¹⁴C, ¹³C, ‐ (RS) mevalonolactone (¹⁴C₂‐4,5) et (RS) mevalonolactone (¹⁴C‐5)

Abstract

Three new routes t 3 (RS) mvalonolactone s u i t a b l e for the double labeling w i t h i s o t o v i c carbon a t p o s i t i o n s 4 and 5 or labelinga t C-5 are out lined. 1-(2,4.1O-trioxaadamantyl) propanone : -2 was prepared from 2 -( 2 . 4 , 10-tm-oxaadamantuli acetylchloride I and b i s -( t r i m e t h y l s i l u 2 ) malonate. Addition of [ 1 4 C 2 ] -e t h i n y i l i t h i m o i 2 provided an 80 % y i e l d of a c e t y l e n i c alcohol : 2. The l a t t e r was submitted t o the r e g i o s e l e c t i v e gem terminal Sishydroboration with 9-BBN followed by oxidation w i t h hydrogen peroxide and base leading t o the 1.3-diol : l a t i o n gave [4,5 " C 2 ] rnevaZonolact&e : 48 ' % overall y i e l d based on Ba l4CO3s p e c i f i c a c t i v i t y 98.5 mCi/mM. A second route following the same p a t t e r n started from c o m e r c i a l 1 , l dimethoxy 3-butanone : -6. Addition of p 4 C 2 ] ethiny l l i thium with 6 gave the alcohol with hydrogen peroxide and base leading t o t4e 1,d-diol which a f t e r chromatography was oxidized with bromine uater i n hydrochZor& z i i d provided [4,5 Cd aevalonolactone. This route was followed t o provide I0 gm batches o f p,S-i37?] mevalonolactone. The t h i r d scheme involved the condensation of e t h y l l i t h i o [1-14C] acetate with ketone : 2 followed by reduction w<th !;iAZ$J of the resLLIt i n g 6hydro -ester 9 i n t o 1,3 d i o l : la Jhich by hydrochloric hbdrolysis gave r i s e t o 7 -1 4 C l mevalonolactone -: 50 % overall y i e l d based on e t h u i acetate : s p e c i f i c a c t i v i t y : 50 mCi/mMole. the hudrolysis of which, without isowhich was treated with 9-BBN followed by m i d a t i o n 14 ---L ' a c i d e mevalonique e t sa l a c t o n e 5j o u e n t un r61e i m p o r t a n t dans l a biosynthese des terpPnes, s t e r o i d e s e t a u t r e s substances n a t u r e l l e s ( l a ) x Address any correspondence t o t h i s a u t h o r .

Preparation of Carbon‐14‐Labeled Compounds via the [ 14 C 2 ]Acetylene Tree

“…Chain extension through aldol condensation with acetone and acid-catalyzed cyclization converted 7 to b- [6,7-14 C 2 ]ionone. Bis-hydroboration of [ 14 C 2 ]alkynol 9 with 9-borabicyclo[3.3.1]nonane, oxidative work up and hydrolytic cleavage of the carboxylic acid protecting group provided racemic [4,[5][6][7][8][9][10][11][12][13][14] C 2 ]mevalonolactone 6 (10). Bis-hydroboration of [ 14 C 2 ]alkynol 9 with 9-borabicyclo[3.3.1]nonane, oxidative work up and hydrolytic cleavage of the carboxylic acid protecting group provided racemic [4,[5][6][7][8][9][10][11][12][13][14] C 2 ]mevalonolactone 6 (10).…”