John C. Rohloff

Practical synthesis of the anti-HIV drug, PMPA

Abstract The anti-HIV nucleotide analogue PMPA can be prepared on a kilogram-scale by a three step sequence: i) condensation of adenine with ( R )-propylene carbonate, ii) alkylation of the resulting ( R )-9-(2-hydroxypropyl)adenine with diethyl p -toluenesulfonyloxymethanephosphonate using lithium tert -butoxide and iii) cleavage of the phosphonate ester functionalities with bromotrimethylsilane.

Bromonitrile oxide [3+2] cycloadditions in water

Abstract Bromonitrile oxide can be generated homogeneously in water at acidic pH, allowing efficient [3+2] cycloaddition with water soluble olefins and acetylenes. Allylammonium salts react with high regioselectivity and without the need for N-group protection.

Enantioselective synthesis of 5-LO inhibitors using a gulofuranose auxiliary

Abstract The pure R-(+)-enantiomer of 5-lipoxygenase inhibitor Zileuton was prepared by diastereoselective methyl Grignard addition to an aldonitrone bearing a D-gulofuranose-derived chiral auxiliary. Addition of the Lewis acid trimethylaluminum leads to a reversal of the alkylation stereochemistry and the potent pyrido analogue, R-(+)-RS-27871 was prepared in this way from an L-gulofuranose-derived nitrone.

Facile chemical synthesis of S,S-isodityrosine, a naturally-occurring cross-linking amino acid

Ullmann coupling of the two protected S-tyrosine derivatives 6 and 9 afforded the protected isodityrosine 10 which was converted into the natural bis-amino acid S,S-isodityrosine 1 in good yield.

General preparation of 3-alkyl-1-naphthols

Potassium enolates derived from readily available o-alkynylacetophenones undergo intramolecular cycloaromatization on heating to afford 3-alkyl-1-naphthols in good yields.

IMPROVED PREPARATION OF (R) AND (S)-3-AMINOQUINUCLIDINE DIHYDROCHLORIDE

Abstract An improved procedure for the synthesis of either (R) or (S)-3-aminoquinuclidine was developed. Key intermediate imine 2 was made in a one pot process using lithium oxide as the base and molecular sieves.