Daniel P. Getman

Synthesis of 1,3-dideoxy-3-fluoronojirimycin

Novel compounds represented by the formula: ##STR1## wherein R represents hydrogen, optionally substituted alkyl radicals having from 1 to about 10 carbon atoms, optionally substituted alkenyl radicals having from 1 to about 10 carbon atoms, optionally substituted aryl, alkaryl and aralkyl radicals having from about 6 to about 16 carbon atoms and optionally substituted acyl and acyloxy radicals having from about 1 to about 10 carbon atoms, manifest glycosidase inhibition activity.

Influence of polyfluorination of the phenylalanine ring of angiotensin II on conformation and biological activity

[Phe(F5)8]angiotensin II was synthesized by the solid phase method and purified by reverse-phase HPLC. In rat uterus and rabbit aorta bioassays the analogue had 10 and 50%, respectively, of the contractile activity of angiotensin II and demonstrated antagonist properties. These findings illustrate that inversion of the Phe8 ring quadrupole moment in angiotensin II decreases agonist activity and invokes antagonist properties. 1H-NMR studies at 400 MHz in DMSO-d6 demonstrated the presence of cis and trans isomers in the ratio 1:3 due to restricted rotation of the His-Pro bond. Downfield shifts of the His C2 and C4 protons in [Phe(F5)]ANG II compared to ANG II suggest that the Phe(F5) residue may be involved in a parallel-plate ring pairing interaction with the imidazole group. However heteronuclear NOE studies, carried out by measuring the proton difference spectrum before and after saturation of the fluorine resonances, showed the absence of any NOE enhancement illustrating that electrostatic influences of the Phe(F5) ring occur at relatively long range.

Selective functionalization of the C2 hydroxyl group of N-carbobenzyloxy-4,6-O-benzylidene-1-deoxynojirimycin

1-Deoxynojirimycin was converted into its N-CBZ-4,6-O-benzylidene derivative 2 in two steps in 51% yield. Compound 2 could be regioselectively functionalized at the C2 hydroxyl group by activation with di-n-butyltin oxide, followed by reaction of the resulting stannylene with electrophiles. In this manner, the 2-O-benzoyl and 2-O-tosyl analogs could be obtained in yields of 73% and 94%, respectively.