Asymmetric synthesis of tertiary and quaternary allyl- and crotylsilanes via the borylation of lithiated carbamates

Tertiary allyl- or crotylsilanes have been prepared in high er and dr via the lithiation-borylation reaction of alkyl carbamates with silaboronates. Using a related strategy, quaternary allylsilanes could be accessed in similarly high er.     

Total synthesis of (+)-erogorgiaene using lithiation-borylation methodology, and stereoselective synthesis of each of its diastereoisomers

A short (8 steps) synthesis of (+)-erogorgiaene in 44% overall yield from p-methylacetophenone is described. Key steps include lithiation/borylation-protodeboronation to build up the molecule and control the stereochemistry at C1 and C4. The C11 stereochemistry was similarly set up by using lithiation/borylation methodology. The use of a mixed, unhindered borane in the lithiation/borylation reaction proved critical to success in the reaction of the tetralone-derived carbamate to control the C4 stereochemistry. The power of the reagent controlled methodology is illustrated in the stereocontrolled synthesis of all of the diastereomers of (+)-erogorgiaene.     

DISTRIBUTION AND ELIMINATION OF PHOTOFRIN II IN MICE

The distribution and elimination of [14C]PII, the radioisotopically-labeled equivalent of the mixture of porphyrins known as Photofrin II used in the photodynamic treatment of solid tumors, were determined in tumor-free and SMT-F tumor-bearing DBA/2 Ha-DD mice. Following i.p. injection, drug was absorbed from the peritoneum with a half-life of about 1 h; elimination from plasma was rapid, declining about 1.4 logs in concentration over 48 h following i.v. administration. However, some [14C]-activity was still detectable after 75 days. Normal tissues take up the drug within about 7.5 h after administration, with peak concentrations distributed as follows: liver, adrenal gland, urinary bladder greater than pancreas, kidney, spleen greater than stomach, bone, lung, heart greater than muscle much greater than brain. Only skeletal muscle, brain, and skin located contralaterally to subcutaneously implanted SMT-F tumors had peak [14C]-activities lower than tumor tissue; skin overlying SMT-F tumors showed concentrations not significantly different (P greater than 0.3) from tumor. After 75 days all tissues examined retained some fraction of [14C]-activity, ranging from 16% for kidney to 61% for spleen, of the initial peak tissue levels. The primary route of elimination of Photofrin II was through the bile-gut pathway, with greater than 59% of the administered [14C]-activity recovered in the feces, and only about 6% in the urine, over 192 h. HPLC analyses of fecal extracts showed that mostly monomeric and other low molecular weight porphyrin components of Photofrin II were eliminated. The higher molecular weight oligomeric fractions of Photofrin II were retained in liver and spleen up to 14 days after injection.     

SEARCH FOR SINGLET OXYGEN LUMINESCENCE IN THE DISPROPORTIONATION OF HO2/O2

Abstract— During the reaction HO₂+ HO₂ (or O₂^-) = H₂O₂+ O₂ in aqueous solution, no luminescence in the region 620–720 nm, expected if the product O₂ were formed in a singlet state, could be detected. If any singlet O₂ is formed, its yield must be less than 10%. Faint luminescence, sometimes found at shorter wavelengths, was shown to arise from reaction of HO₂ with impurities in the reagents present.     

Facile Regioselective On-Water Synthesis of 4,7-Dihydropyrazolo[1,5-a]Pyrimidines and 4,7-Dihydro[1,2,4]Triazolo[1,5-a]Pyrimidines

Chemistry of Heterocyclic Compounds - Efficient and regioselective on-water synthesis of variously substituted 5-amino-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carbonitriles and...     

Theoretical studies on conformational preferences of modified nucleic acid base N6-(N-glycylcarbonyl) adenine

Conformational preferences of modified nucleic acid base N⁶-(N-glycylcarbonyl) adenine, gc⁶Ade, have been investigated using the quantum chemical PCILO (Perturbative configuration interaction using localized orbitals) method. The multidimensional conformational space has been searched using selected grid points formed by combining various torsion angles that take favored values derived from energy variation with respect to each torsion angle individually. The theoretically predicted most stable, minimum energy conformation of the molecule is such that the substituent on N(6) spreads away from the imidazole moiety of the adenine ring, thus keeping distal orientation. The preferred molecular orientation is stabilized by an intramolecular hydrogen bond from N(11)H of the amino acid to N(1) of the adenine. The carboxylic group of the substituent is trurned away in relation to N(11)H…?N(1) and is perpendicular to the plane through the rest of the molecule The alternative stable conformation corresponding to an 0.8 kcal/mol higher energy has a coplanar carboxylic group turned towards the same side as N(11)H…?N(1) and is exhibited in the crystal structure of the nucleoside derivative, gc⁶A. Energetically, the carboxyl group may change its orientation over a wide range, without much destabilization. This suggests probing by the carboxyl group of the molecular environment in the vicinity of the anticodon in tRNA.     

Synthesis of novel benzo[h][1,6]naphthyridine derivatives from 4-aminoquinoline and cyclic β-ketoester

This paper describes the synthesis of 2,8-dichloroquinolin-4-amine 4 and 4,5,7-trichloro-3-(2-chloroethyl)-2-methylbenzo[h][1,6]naphthyridine 8 as novel class of building blocks. Also describes the regioselective S_NAr reactions of 2,4,8-trichloroquinoline 2 on C₂ and C₄ positions with azide, similarly S_NAr reactions of benzo[h][1,6]naphthyridine 8 at C₄, C₅ positions, and S_N2 reactions on C₃-(2-chloroethyl) side chain with nucleophiles such as primary aromatic amines, methoxide/ethoxide, and azide at different temperatures.     

Geometry and quadratic nonlinearity of charge transfer complexes in solution: a theoretical study

In this paper, we have computed the quadratic nonlinear optical (NLO) properties of a class of weak charge transfer (CT) complexes. These weak complexes are formed when the methyl substituted benzenes (donors) are added to strong acceptors like chloranil (CHL) or di-chloro-di-cyano benzoquinone (DDQ) in chloroform or in dichloromethane. The formation of such complexes is manifested by the presence of a broad absorption maximum in the visible range of the spectrum where neither the donor nor the acceptor absorbs. The appearance of this visible band is due to CT interactions, which result in strong NLO responses. We have employed the semiempirical intermediate neglect of differential overlap (INDO∕S) Hamiltonian to calculate the energy levels of these CT complexes using single and double configuration interaction (SDCI). The solvent effects are taken into account by using the self-consistent reaction field (SCRF) scheme. The geometry of the complex is obtained by exploring different relative molecular geometries by rotating the acceptor with respect to the fixed donor about three different axes. The theoretical geometry that best fits the experimental energy gaps, β(HRS) and macroscopic depolarization ratios is taken to be the most probable geometry of the complex. Our studies show that the most probable geometry of these complexes in solution is the parallel displaced structure with a significant twist in some cases.