Processes for preparing macrolides and ketolides and intermediates therefor

Content Provider	Semantic Scholar
Author	Перейра, Дэвид Е.
Copyright Year	2011
Abstract	FIELD: chemistry. SUBSTANCE: invention described herein relates to methods of obtaining macrolide antibacterial agents. In particular, invention relates to methods for preparing macrolides and ketolides from erythromycin A. Method of producing a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 10 is hydrogen or acyl; X is H; Y is OR 7 ; where R 7 is cladinose, alkyl or arylalkyl, or acyl or C(O)NR 8 R 9 , where each R 8 and R 9 is independently selected from a group, consisting of hydrogen, hydroxy, alkyl, alkoxy, aryl, aryalkyl, dimethylaminoalkyl, acyl, sulphonyl, ureido and carbamoyl; or R 8 and R 9 together with nitrogen atom attached thereto form a heterocycle; or X and Y together with a carbon atom attached thereto form a carbonyl; V is C(O), C(=NR 11 ), CH(NR 12 , R 13 ) or N(R 14 )CH 2 ; where N(R 14 ) is bonded to C-10 carbon atom; where R 11 is a hydroxy or alkoxy; each R 12 and R 13 is independently selected from a group consisting of hydrogen, hydroxy, alkyl, alkoxy, aryl, aryalkyl, dimethylaminoalkyl, acyl, sulphonyl, ureido and carbamoyl; R 14 is hydrogen, hydroxy, alkyl, alkoxy, aryl, arylalkyl, dimethylaminoalkyl, acyl, sulphonyl, ureido or carbamoyl; W denotes H, F, Cl, Br, I or OH; A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH or C(O)NHS(O) 2 ; B is (CH 2 ) n , where n is an integer from 0 to 10; or unsaturated carbon chain, containing from 2 to 10 carbon atoms; and C is hydrogen, hydroxy, alkyl, alkoxy, aryl, arylalkyl, acyl, acyloxy, sulphonyl, ureido or carbamoyl; where alkyl independently in each case represents a C 1 -C 30 alkyl; aryl in each case is independently selected from a group consisting of phenyl, optionally substituted amino group, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, quinolinyl, quinazolinyl, quinoxalinyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, benzisoxazolyl, benzisothiazolyl; acyl in each case is independently selected from a group consisting of C(O)alkyl and C(O)aryl, C(O)arylalkyl; involves (b) bringing a compound of formula (IV) or acid addition salt thereof, where R is a spatially hindered acyl group; and Q is 2-methoxy-2-propyl, 1-methoxycyclohexyl or tropyl; into contact with a methylating agent to obtain a compound of formula (V) or acid addition salt thereof; and (c) bringing compound of formula (V) or acid addition salt thereof into contact with deoximating agent to obtain a compound of formula (II) or acid addition salt thereof; and conversion of compound of formula (II) or acid addition salt thereof into a compound of formula (I) or a pharmaceutically acceptable salt thereof. EFFECT: production of antibacterial agents. 32 cl, 9 ex
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Language	English
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Content Type	Text
Resource Type	Article