The stereochemistry of beta-lactam formation in penicillin biosynthesis.
1. (2R,3S)-[U-14C,3-3H1]- and (2R,3R)-[U-14C,2,3-3H2] Cysteine hydrochlorides have been separately synthesised. The latter compound has been shown to have uniform distributions of tritium between C-2 and C-3. 2. The abvoe cysteines and (2R)-[U-14C,3,3,3',3'-3H4]cystine have been converted to samples of penicillin G by Penicillium chrysogenum. 3. Incorporation results indicate that all but 14% of the tritium is lost from the (2R,3S)-[3-3H1]isomer; that 42% of tritium is retained by the non-stereospecifically C-3 tritiated cystine; and that 58% of tritium is retained by the (2R,3R)-[2,3-3H2]isomer on conversion to penicillin G. 4. Degradation of the penicillin G derived from (2R,3R)-[U-14C,2,3-3H2]cysteine hydrochloride has indicated that in fact about 87% of the original C-3 tritium of cysteine is retained at C-5 of penicillin G. 5. The results indicate stereospecificity in the cyclisation giving rise to the beta-lactam ring in penicillin G in nature with loss of the 3-pro-S-hydrogen and rentention of the 3-pro-R-hydrogen of cysteine. Thus there is net retention of stereochemistry in the cyclisation.
D002250:Carbon Radioisotopes; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009904:Optical Rotation; D010400:Penicillin G / Q000378:metabolism; D010406:Penicillins / Q000096:biosynthesis; D010408:Penicillium chrysogenum / Q000378:metabolism; D013237:Stereoisomerism; D014316:Tritium; D047090:beta-Lactams
D002250:Carbon Radioisotopes; D010406:Penicillins; D047090:beta-Lactams; D014316:Tritium; D010400:Penicillin G