Sean P. McKee

An efficient synthesis of hydroxyethylene dipeptide isosteres : the core unit of potent HIV-1 protease inhibitors

An efficient and stereocontrolled synthesis of hydroxyethylene dipeptide isosteres 1 from commercially available, optically pure D-mannose is described. This synthesis represents a practical and enantioselective entry to a range of other dipeptide isosteres, which are not limited to amino acid derived substituents.

Stereoselective reduction of α-hydroxy oxime ethers: a convenient route to cis1,2-amino alcohols

Reduction of cyclic α-hydroxyketoximes with borane provides an excellent, high yielding, regio- and stereoselective route to CIS-1, 2-amlnoalcohols.

Potent HIV-1 protease inhibitors: stereoselective synthesis of a dipeptide mimic

The synthesis of a differentially protected dipeptide mimic 10 in enantiomerically pure form is described. The key step involves the epimerization of the C-2 center of the lactone 4, hydrolysis and protection of the resulting hydroxy acid, followed by Curtius rearrangement to introduce the urethane functionality. The scope and versatility of this isostere has been demonstrated by its conversion to potent HIV-1 protease inhibitors with nanomolar potencies. Also, established through the synthesis of compound 13 and 14, the 3S hydroxyl configuration of the dipeptide isostere 1 is the preferred configuration for its potency. The present synthesis is efficient and provides an access to other dipeptide mimics with a great deal of structural diversity.

Di(2-pyridyl) carbonate promoted alkoxycarbonylation of amines: A convenient synthesis of functionalized carbamates

The reaction of di(2-pyridyl) carbonate with a variety of alcohols including hindered secondary, tertiary and protected glycols afforded the corresponding mixed carbonate which was efficiently transformed into various carbamates in high yield under mild conditions.

Stereocontrolled synthesis of HIV-1 protease inhibitors with C2-axis of symmetry

An efficient and stereocontrolled synthesis of various C2-symmetric HIV-l protease inhibitors is described, starting from commercially available and inexpensive D-mannitol.

A facile and enantiospecific synthesis of 2(S)- and 2 (R)[1′(S)-azido-2-phenylethyl]oxirane

The title azidoalkyl oxiranes were synthesized efficiently in an enantiomerically pure form utilizing readily available diethyl d-tartrate.

An efficient synthesis of functionalized urethanes from azides

Catalytic hydrogenation of various azides in the presence of functionalized mixed carbonates afforded the corresponding urethanes in high yields.

Highly enantioselective aldol reaction: development of a new chiral auxiliary from cis-1-amino-2-hydroxyindan

Boron enolates obtained from optically active oxazolidinone derivative of cis-1-amino-2-hydroxyindan are reacted with various aldehydes to provide highly enantioselective aldol products in good yields.