Thomas N. Salzmann

A novel synthesis of the carbapen-2-em ring system

Abstract A new synthesis of the carbapenem ring system, as found in thienamycin and related natural products, has been developed. The key step involves a highly efficient carbene insertion reaction which produces the bicyclic ring system by forming the N3 bond.

Total synthesis of (−) homothienamycin

Abstract The total synthesis of a ring expanded analog of thienamycin has been developed. The key step utilizes a highly efficient carbene insertion reaction to form the carbacephem ring system.

A new approach to the diastereoselective synthesis of aldols:Introduction of the 6α-(1R-hydroxyethyl) side chain of the carbapenem and penem antibiotics

Abstract The 6 α-(1 R -hydroxyethyl) side chain has been introduced via a stereocontrolled aldol reaction with a silyl ketone as a hindered acetaldehyde equivalent. The derived trans-S silyl carbinol undergoes a completely stereospecific rearrangement to the desired trans-R O-silyl ether. The two-step sequence may be done in one-pot in overall yields of 70–90%.

2-Naphthylcarbapenems: Broad spectrum antibiotics with enhanced potency against MRSA

A regioisomeric set of 2-naphthylcarbapenems featuring cationic substituents was synthesized. Optimal placement of the cationic group was found to markedly improve activity against methicillin-resistant staphylococci while maintaining a good spectrum of gram-negative activity.

The discovery and synthesis of 2-biphenylcarbapenems active against methicillin resistant staphylococci

Abstract The discovery and synthesis of the arylcarbapenem 2b possessing potent activity against highly resistant strains of methicillin resistant staphylococci are dislosed.

The synthesis and antibacterial activity of 2-para-quarternary ammoniomethylphenyl-carbapenems.

Abstract The synthesis and in vitro antibacterial activity of 2-phenylcarbapenems bearing a spacer linked heteroaromatic or heterocyclic quaternized moiety are discussed. In general, this class of antibiotics was found to possess antibacterial activity superior to the parent natural product, thienamycin, except for Ps. aeruginosa , and were less susceptible to degradation by the DHP-I enzyme.