Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats.

1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42-46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.

Regioselective iodoazidation of alkynes: synthesis of α,α-diazidoketones.

Aryl alkyl alkynes reacted with N-iodosuccinimide (NIS) and trimethylsilyl azide (TMSN3), leading to α,α-diazidoketones via the regioselective addition of IN3 to alkynes. Huisgen cyclization of α,α-diazidoketones generated bis-triazole compounds.

Ligand-promoted asymmetric imino-Reformatsky reaction of ethyl dibromofluoroacetate.

An enantioselective Reformatsky reaction has been developed for the reaction of ethyl dibromofluoroacetate (1) with an imine. This method represents the first ligand-promoted imino-Reformatsky approach to use a halofluoroacetate. The use of an amino alcohol ligand allowed for the preparation of enantioenriched α-bromo-α-fluoro-ß-lactams in good yields with enantioselectivities up to 96% ee. This process also provided access to ß-lactam rings bearing two stereogenic centers.

Regio- and stereoselective multisubstituted enol ester synthesis.

Regio- and stereoselective cohalogenation of alkynes with NXS (X = Br, I) was achieved, and the stereoselectivity of the resulting alkenes was dependent on the substituent on the alkyne. Cohalogenation and successive cross-coupling gave multisubstituted enol esters in a one-pot process.

Indium(III)-catalyzed tandem reaction with alkynylbenzaldehydes and alkynylanilines to heteroaromatic compounds.

Starting from ortho-alkynylbenzaldehydes and ortho-alkynylanilines, In(OTf)3-catalyzed synthesis of ring-condensed heteroaromatic compounds was developed via a domino intramolecular nucleophilic attack/intermolecular cycloaddition/dehydration reaction.

CD spectral study of Dnp derivatives of amino acids and peptides for their configurational and conformational analysis.

Rules relating the stereochemistry of N-Dnp (Dnp: 2,4-dinitrophenyl) derivatives of alpha-amino acids and peptides and the sign of the Cotton effects at the longest wavelength band (ca. 400 nm) are surveyed. Some new data and insights concerning the CD spectra of Dnp-alpha-amino acids are included: i.e., the spectra of Dnp derivatives as the composite of the corresponding o-nitrophenyl and p-nitrophenyl derivatives; the crystal structure of Dnp-I-phenylalanine and its solid-state CD spectra; the CD spectra of Dnp-alpha-amino acids containing sulfur atom on their side chains; and the theoretical approach to the CD spectra using molecular orbital method-based calculation. Conformational analyses of cyclic and linear peptides by the CD spectra of their Dnp derivatives are also discussed.

Molecular assembly of C2-symmetric Bis-(2S)-2-methyldodecanoylamides of alpha,omega-alkylidenediamines into coiled coil and twisted ribbon aggregates.

A series of 10 didodecanoylamides of alpha,omega-alkylidenediamines bridged by a straight carbon chain varying in length from 0 to 9 carbons was examined as possible gelator molecules of organic liquids to gain information on the relationships between the spacial arrangement of two amide groups in a molecule and their effects on the microscopic structures of the gel. The structural characteristics of these amides are parallel and antiparallel arrangements of two amide carbonyl groups, which depend on the even and odd numbers of a bridging zigzag carbon chain. The linear alkyl chain moieties and a center carbon chain of diamides intermolecularly interact with each other within the van der Waals contact. Two amide moieties of an even number carbon chain diamide intermolecularly interact with each other by using two pairs of hydrogen bonds with two other molecules in a plane, which formed ribbonlike self-complementarily assembled aggregates. On the other hand, a diamide of an odd number carbon chain forms four independent hydrogen bonds with four other molecules not in a plane, which assembled into woven aggregates. Asymmetric introduction of a methyl group at the alpha-position of the amide groups successfully twists the two side chain van der Waals cores of the chiral diamides in the fixed direction, giving helically twisted ribbon and coiled coil aggregates. The helically twisted ribbon and coiled coil aggregates of these chiral diamides were directly observed by CD, SEM, and TEM, providing a basis for the design of a sophisticated small molecular gelator of a tailor-made shape.

Crystal structure of acetyl 29-methyl-29-methylidene-D:C-friedoolean-8-en-3beta-ol.

Acetyl 29-methyl-29-methylidene-D:C-friedoolean-8-en-3beta-o1 (2), derived from bryonolic acid (D:C-friedoolean-8-en-3beta-ol-29-oic acid) (1), was crystallographically analyzed. Rings A-E of 2 adopted chair, half-chair, half-chair, boat (with bow and stern at C-13 and C-16), boat (with bow and stem at C-19 and C-22) conformations, respectively. Good agreement was found between the structures from X-ray crystallography and that from MM2 calculations.

Radical addition of ethers to imines initiated by dimethylzinc.

Ethers undergo addition to imines in the presence of dimethylzinc and air through a radical process. [reaction: see text]

Relative stabilities of some synthetically useful 2,3-cis-disubstituted aziridines and their 2,3-trans isomers.

The relative stabilities of synthetically useful 2,3-cis/trans pairs of 2,3-disubstituted aziridines were investigated theoretically by performing molecular orbital calculations at the MP2/6-31G**/RHF/6-31G** level of theory. The results showed clearly that a functional group on the nitrogen atom of the aziridine ring plays a very important role in conjunction with the relative stabilities of these pairs of isomers. There is a tendency that the 2,3-cis isomer bearing tetrahedral structure on the aziridine nitrogen is preferable. Bulky substituents such as a phenyl group on aziridine atoms can also affect the relative stability sterically.

Palladium(0)-Catalyzed Isomerization Reactions of Aziridines Bearing an alpha,beta-Unsaturated Ester Group: A Thermodynamic Preference for Chiral Alkyl (2E)-4,5-cis-4,5-Epimino-N-(alkyl- or arylsulfonyl) 2-Enoates over the Other Three Stereoisomers.

Palladium(0)-catalyzed reactions of five sets of four stereoisomeric 4,5-epimino-N-(methanesulfonyl) or -N-(arylsulfonyl) 2-enoates reveal that 4,5-cis-(2E)-isomers are thermodynamically more stable than other isomers, in accord with calculations. A highly stereoselective synthesis of (E)-alkene dipeptide isosteres having the desired stereochemistries from unwanted stereoisomeric 4,5-epimino-N-(arylsulfonyl) 2-enoates is also presented.