| 摘要 |
<p>(A) Prepn. of penam derivs. of formula (IV) comprises: (a) reacting an azetidinone deriv. of formula (I) with a molar excess of silver nitrate in presence of molar excess of pyridine in an inert solvent at -25 to +25 deg. C, then treating with hydrogen sulphide to give an azetidine deriv. of formula (II); (b) acylating with 1 molar equiv. of p-nitrophenyl chloroformate in presence of 1 molar equiv. 4-(dimethylamino)pyridine in an inert solvent at -25 to + 25 deg. C to give an azetidinone of formula (III); and (c) reacting with molar excess of lithium hexamethylolsilylamide at -50 to -100 deg. C to give (IV); where R = CH2CX=CH2, CH2CH2SiMe3, p-nitrobenzyl or ester forming gp. which is hydrolysable in vivo; X = H or Cl; R1 = silyl protecting gp. (IC) may then be: (d) reacted with 1 molar equiv. triflic anhydride in presence of a molar excess of diisopropylethylamine in an inert solvent at -40 to -90 deg. C to give a soln. of a cpd. of formula (V); and either: (e) reacted with at least 1 molar equiv. of HSR2 at 0 to -90 deg. C to give a penem of formula (VI); or (e') reacted with at least 1 molar equiv. of (R6R5CH)2Cu(CN)nLin+1 at -60 to -100 deg. C to give a penem of formula (VI'); Where R2 = e.g. 1-4C alkyl, (1,3-dioxacyclopent-4- or 2-yl)methyl, (2-oxo-1,3-dioxa cayclopent-4-yl)methyl, (1-methyl-2-imidazolyl) methyl, etc.; Q = OH, p-nitrobenzyloxycarbonylamino, piperidino, pyrrolidino, morpholino or 4-allyloxycarbonylpiperazino; R5 = H or 1-8C alkyl; R6 = H, Me, 1-8C alkoxy or OR7; R7 = hydroxyprotecting gp.; or R5 + R6 = (CH2)mO(CH2)p; m and p = 0-5; provided that m + p is at least 3; and n = 0-1.</p> |
