Simultaneous hydrogenolysis of p-nitrobenzyl esters and carbamates side-chains in the THF 1beta-carbapenem OCA-983 in biphasic media.
Deprotection of p-nitrobenzyl esters and valyl carbamates in carbapenem CL 192,276 produced the active compound OCA-983 in excellent yields. Straight chain alkanols such as 1-butanol, 1-pentanol and 1-hexanol in water at certain ratios were effective solvent systems. Alkyl acetates in water also resulted in simultaneous deprotection of PNB and PNZ side-chains albeit at slower rates. The deprotected carbapenem was isolated in excellent yield and purity after removal of the aqueous media. This procedure is applicable to sensitive compounds that are soluble in water without the need to use a buffer and allows for ease of isolation from the aqueous phase.
Mansour
Tarek S
TS
Medicinal Chemistry, Chemical and Screening Sciences, Pearl River, NY 10965, USA. mansout@wyeth.com
Sum
Phaik-Eng
PE
Lin
Yang-I
YI
How
David
D
Li
Zhong
Z
D000085:Acetates / Q000737:chemistry; D000438:Alcohols / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry*; D015780:Carbapenems / Q000138:chemical synthesis* / Q000494:pharmacology; D004952:Esters / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D015394:Molecular Structure; D009578:Nitrobenzenes / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000085:Acetates; D000438:Alcohols; D000900:Anti-Bacterial Agents; D002219:Carbamates; D015780:Carbapenems; D004952:Esters; D009578:Nitrobenzenes; C513391:OCA-983; D012997:Solvents; D014867:Water; D006859:Hydrogen