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Research conducted on a new one-step cyclization method to provide 2,5-distributed pyrrolidine stereoisomers in an enantiomerically pure form is presented. The authors discuss the basic principle of the method.

alpha,beta-Unsaturated esters or nitroalkenes were reacted with oxazoline N-oxide to produce the corresponding adducts. The high regio- and stereoselectivities of the adducts were found to be a function of the substitution pattern on the dipolarophile. Inversion of regioselectivity resulted from the switching from a 1,2-disubstituted to a 1,1-disubstituted alpha,beta-unsaturated ester.

The first-ever application of the Zincke reaction to the enantioselective syntheses of 1-substituted 1,2-dihydroisoquinolines, 1- or 3-substituted 1,2,3,4-tetrahydroisoquinolines and 1,3-disubstituted 1,2,3,4-tetrahydroisoquinolines is described. These new chiral isoquinolinium salt derivatives were produced in good yield and in moderate to good diastereoisomeric excess. Results affirmed the utility of the approach in the synthesis of polysubstituted tetrahydroisoquinolines.

The photochemical behavior of single-stranded peptide nucleic acids (PNAs) and their analogues are compared, incorporating a 4-mercaptopyrimidine at their C- or N-end. Results indicate that most of all biological photoadducts can be physiologically repaired by their respective specific photolyases. Findings also show that some adducts which are naturally occurring nucleic acid photoproducts can also undergo a spontaneous repair process under mild acidic pH conditions.

A novel synthetic pathway was developed for the production of optically pure cis- and trans-3-substituted proline derivatives based on an enantio- and stereoselective route. The method involves the formation of optically pure proline derivatives via a stereodivergent route. Furthermore, the stereocontrolled synthetic process can also be utilized for the synthesis of lithiated species with high stereofacial selectivity.

A stereogenic center is synthesized by the Michael-type addition of chiral imines to alpha- and beta-substituted alkenyl acceptors. The reaction is highly regio- and stereoselective. The alkylation takes place mainly at the more substituted alpha-end of the imine on the less hindered pi-face. The Michael acceptors, excepting methyl propiolate, allow control of the configuration of the adducts. The reaction involves the transfer of the hydrogen atom of the enamine's nitrogen center to the alpha-vinylic carbon atom of the acceptor. This is accompanied by the formation of a C-C bond.

Experiments and molecular mechanics computations were performed to examine the electronic and structural factors that determine the Diels-Alder reactivity and regiochemistry of N-phenyl-2-cyano-1-azadienes. N-phenyl-1-aza-2-cyano-1,3-butadiene was subjected to (4 + 2) cycloadditions with dienophiles such as methyl vinyl ketone, styrene and ethyl(methyl)vinyl ether at 90-120 degrees Celsius. The results showed that the 1-azadienes undergo an endo cycloaddition.

N-acetyl and N-Cbz derivatives of (1S,4S,5R)-4-(methoxycarbonyl)-3-oxa-6-azabicyclo(3.1.0)hexan-2-one from D-ribose have been synthesized. Analysis of subsequent reactions revealed the first use of a carbohydrate for the preparation of L-glutamate derivatives and the first example of a stereocontrolled synthesis of glutamate analogues.

A study was conducted on the simple and fast preparation of the bicyclic core structure of the enediyne antibiotic esperamicin-A1 in both enantiomeric forms of the beta,gamma-unsaturated ketone. Inexpensive and readily available (-)-quinic acid was used as the common starting material. Aziridine was easily produced and converted to its carbamate derivative in preparation for aziridine ring opening.

X-ray crystallographic studies of the structure of a chiral auxiliary crotonate reveal that the auxiliary molecule contains two pi-systems near each other in a coplanar geometry. Michael addition reaction of diphenylmethaneamine to the crotonate, yielding a crotonate adduct, is highly M-face selective. NMR spectra reveals that the crotonate has shielded protons.

A protocol for the production of desired AZT analogs and a novel 1'-azido-substituted-2'-deoxyxylose derivative is described. The process is based on the idea that access may be achieved through quaternization of the N3 imino ether nitrogen in anhydronucleoside, followed by reaction of the generated salt with NaN3. The reaction was started with 5'-O-(thexyldimethylsilyl)anhydronucleoside and MSH in CH2Cl2, followed by a change of solvent to DMF. The N3-amino AZT derivative was isolated in 90% yieldafter flash chromatography.

A previously reported, successful synthesis of aristolasicone and 17-epi-aristoteline leads to a restudy and subsequent revision of their structures. The new study reveals these alkaloids, first isolated from Aristotelia australasica, to possess an inverted indole unit, the first natural compounds to do so. Extensive use of X-ray and spectroscopic techniques, including fast atom bombardment, finally yields the correct structures, leading to renaming of the second alkaloid as allo-aristoteline.

Two synthetic routes provide two epimers (8a-alpha-H and 8a-beta-H) of chiral 6,7,8-trihydroxyperhydro(1,3)thiazolo(3,2-a)pyridine, an active analogue of the glycosidase inhibitor castanospermine. Both methods use D-(-)-arabinose as substrate. The first route converts the sugar to a hemiacetal which reacts with aminoethanethiol to yield the epimeric mix. The second converts the sugar to a thiazolidine which undergoes cyclization. The new castanospermine analogues possess remarkable in vitro activity against the HIV virus above 6 micromol, maintaining it at 60% potency up to its cytotoxic level of 500 micromol.

The photochemical reaction between an 'equimolar mixture of 4-thiothymidine and adenosine in water' was characterized via x-ray diffraction studies of the crystal structure of the purine-pyrimidine photoproduct formed. The results suggested that the reaction proceeded through a (2 + 2) cycloaddition in which the thiocarbonyl of 4-thiothymidine saturates the N7-C8 double bond of adenine via a bimolecular reaction.