(2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate: synthesis, absolute configuration, and activity against Cryptosporidium parvum

The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in vivo. It was shown that both the activity and the toxicity are properties of the (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic window there is no advantage in application of one enantiomer over the application of the racemic mixture in the treatment of C. parvum infections.     

Methylenecyclopropane analogues of nucleosides: synthesis, absolute configuration, and enantioselectivity of antiviral effect of (R)-(-)- and (S)-(+)-synadenol.

Synthesis, absolute configuration and antiviral activity of enantiomeric antiviral agents (R)-(-)- and (S)-(+)-synadenol (2 and 3a) are described.     

Total synthesis of (R,R,R)- and (S,S,S)-schweinfurthin F: differences of bioactivity in the enantiomeric series

Total synthesis of the (R,R,R)- and (S,S,S)-enantiomers of the natural product schweinfurthin F has been completed. Comparisons of spectral data and optical rotations with those reported for the natural product, as well as a variety of bioassay data, allow assignment of the natural material as the (R,R,R)-isomer.     

Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation.

Incubation of cholesterol with a bovine adrenocortical mitochondrial acetone-dried powder preparation yielded (22R)-22-hydroxycholesterol (I), (20R,22R)-20,22-dihydroxycholesterol(II), and pregnenolone (III) which were conclusively identified by combined gas chromatography-mass spectrometry. Incubations with [4-14C]cholesterol yielded I, II, and III with specific activities (determined from partial mass-spectral scans) not significantly different from those of the used substrate or the cholesterol reisolated after the incubation, demonstrating that the isolated compounds arose mostly, if not entirely, from the substrate cholesterol. Incubations in an 18O-enriched atmosphere yielded I, II, and III with 18O at position C-22, C-20 and C-22, and C-20, respectively, providing evidence that the hydroxyl groups of the side chain of I and II and the C-20 oxygen atom of III originated from molecular oxygen. The distribution of the oxygen atoms in II after incubation with 18O2 and 16O2 (devoid of 16O18O) proved that the hydroxyl groups of the side chain of II were introduced from two different molecules of oxygen, consistent with a sequential hydroxylation of cholesterol. No (20S)-20-hydroxycholesterol was found. Incubation of I in an 18O-enriched atmosphere afforded II and III with 18O at C-20.     

Practical access to the proline analogs (S,S,S)- and (R,R,R)-2-methyloctahydroindole-2-carboxylic acids by HPLC enantioseparation

An efficient methodology for the preparation of the α‐tetrasubstituted proline analog (S,S,S)‐2‐methyloctahydroindole‐2‐carboxylic acid, (S,S,S)‐(αMe)Oic, and its enantiomer, (R,R,R)‐(αMe)Oic, has been developed. Starting from easily available substrates and through simple transformations, a racemic precursor has been synthesized in excellent yield and further subjected to HPLC resolution using a cellulose‐derived chiral stationary phase. Specifically, a semipreparative (250 mm × 20 mm ID) Chiralpak® IC column has allowed the efficient resolution of more than 4 g of racemate using a mixture of n‐hexane/tert‐butyl methyl ether/2‐propanol as the eluent. Multigram quantities of the target amino acids have been isolated in enantiomerically pure form and suitably protected for incorporation into peptides. Chirality, 2011. © 2011 Wiley‐Liss, Inc.