The relative susceptibility to racemization of L- and D-residues in peptide synthesis

An activated D-residue of a protected dipeptide when coupled racemizes twice as much as an activated L-residue, which is contrary to the case for couplings of acylamino acids.     

Screening of homocysteine from newborn blood spots by high-performance liquid chromatography with coulometric array detection

Homocystinuria, due to a deficiency of cystationine-beta-synthase, refers to the rare inborn error of the metabolism of homocysteine. The identification and prompt treatment of homocystinuria during the neonatal period can prevent or greatly reduce the severity of the clinical consequences. We report a new method for homocystinuria diagnosis from dried blood spots on newborn screening cards, based on high-performance liquid chromatography with electrochemical coulometric array detection. This method shows an excellent linearity (y=10.36x+0.04; r=0.999), precision (RSDs ranged from 2.7 to 5.8%), recovery (87%) and appears to be a cost-effective approach, being simple, rapid, sensitive and cheap.     

Studies in polyphenol chemistry and bioactivity. 4.(1) Synthesis of trimeric,tetrameric, pentameric,and higher oligomeric epicatechin-derived procyanidins having all-4beta,8-interflavan connectivity and their inhibition of cancer cell growth through cell cycle arrest

We report an improved synthesis of bis(5,7,3',4'-tetra-O-benzyl)epicatechin 4beta,8-dimer (3) from 5,7,3',4'-tetra-O-benzylepicatechin (1) and 5,7,3',4'-tetra-O-benzyl-4-(2-hydroxyethoxy)epicatechin (2) by replacing the previously employed Lewis acid, titanium tetrachloride, with the clay mineral Bentonite K-10. Under the same conditions, the benzyl-protected all-4beta,8-trimer, -tetramer, and -pentamer were obtained regioselectively from their lower homologues, albeit in rapidly decreasing yields. Reaction of 2 with an organoaluminum thiolate generated from 2-mercaptobenzothiazole and trimethylaluminum followed by acetylation produced 3-O-acetyl-4-[(2-benzothiazolyl)thio]-5,7,3',4'-tetra-O-benzylepicatechin (12). Medium-sized protected oligomers with 4beta,8-interflavan linkages are obtained in improved yields by using this compound as the electrophile and silver tetrafluoroborate as activator and are isolated by reversed-phase HPLC. Their deprotection by ester saponification followed by hydrogenolysis yielded the free procyanidins, which were characterized as their peracetates. The synthetic procyanidins are identical by normal-phase HPLC with fractions isolated from cocoa. The principle of chain extension by two members was demonstrated using a dimeric electrophile obtained by self-condensation of compound 12. Both the synthetic and natural pentamer 32 inhibit the growth of several breast cancer cell lines. Using the MDA MB 231 line, it was established that this outcome is based on the induction of cell cycle arrest in the G0/G1 phase. Subsequent cell death is more likely necrotic rather than apoptotic. Control experiments demonstrate that the polyphenol itself, rather than hydrogen peroxide potentially formed by its autoxidation, is the causative agent.     

Über die synthese von in position 5 halogenierten,im aromatischen Kern substituierten Valerophenonen

The preparation of 5-chloro-2-methoxy-valerophenone and 5-iodo-2-methoxy-valerophenone proceeding from the -lactone of the corresponding 2-(o-methoxybenzoyl)-5-hydroxy-valeric acid is described.     

Synthesis of 1-Aza-8-thiabicyclo[4.2.1]nona-2,4-diene 8,8-dioxide and its conversion to a strained spirocycle via photoinduced SO2-N bond cleavage

A route to the doubly unsaturated bridgehead sultam 12 has been developed. When irradiated at 350 nm, this conjugated diene is isomerized via a two-photon process to the structurally novel spiro heterocycle 17 constituted of cyclobutene, thietane dioxide, and pyrrolidine rings. A probable mechanism for the generation of 17 and select reactions thereof are reported. [reaction: see text]     

Critical phenomena in polymer mixtures: Monte Carlo simulation of a lattice model

A lattice model of a symmetrical binary (AB) polymer mixture is studied, modelling the polymer chains by self-avoiding walks withN _A =N _B =N steps on a simple cubic lattice. If a pair of nearest neighbour sites is taken by different monomersAB orBA, an energy _ab is won; if the pair of sites is taken by anAA or aBB pair, an energy is won, while the energy is reduced to zero if at least one of the sites of the pair is vacant. To allow enough chain mobility, 20% of the lattice sites are vacancies. In addition to local motions of the chain segments we use a novel grand-canonical simulation technique:A chains are transformed intoB chains and vice versa, keeping the chemical potential difference fixed. The phase diagram is obtained forN=4, 8,16 and 32; the critical behaviour is analysed by finite-size scaling methods. It is shown that the critical exponents are those of the Ising model (=0.32,=0.63) rather than those of the Flory-Huggins meanfield theory (==1/2). Implications of these results for real polymers are briefly discussed.Paper presented at the Frühjahrstagung 1986, Polymerphysik, der Deutschen Physikalischen Gesellschaft, Kaiserslautern, March 12–14, 1986.     

Dynamics of the formation of two-dimensional ordered structures

The growth of ordered domains in lattice gas models, which occurs after the system is quenched from infinite temperature to a state below the critical temperatureT _c, is studied by Monte Carlo simulation. For a square lattice with repulsion between nearest and next-nearest neighbors, which in equilibrium exhibits fourfold degenerate (2×1) superstructures, the time-dependent energy E(t), domain size L(t), and structure functionS(q, t) are obtained, both for Glauber dynamics (no conservation law) and the case with conserved density (Kawasaki dynamics). At late times the energy excess and halfwidth of the structure factor decrease proportional tot ^–x, whileL(t) t ^x, where the exponent x=1/2 for Glauber dynamics and x1/3 for Kawasaki dynamics. In addition, the structure factor satisfies a scaling lawS(k,t)=t ^2xS(kt^x). The smaller exponent for the conserved density case is traced back to the excess density contained in the walls between ordered domains which must be redistributed during growth. Quenches toT>T _c, T=T_c (where we estimate dynamic critical exponents) andT=0 are also considered. In the latter case, the system becomes frozen in a glasslike domain pattern far from equilibrium when using Kawasaki dynamics. The generalization of our results to other lattices and structures also is briefly discussed.     

A case of highly diastereoselective addition to unsymmetrical ketones: lk-addition of (2-alkenyl)triphenoxytitanium derivatives

(2-Butenyl)-, (4-methyl-2-pentenyl)-, and (2-heptenyl)triphenoxytitanium ( 2a – c ) add to dialkyl, alkyl aryl-, and alkinyl aryl ketones to give high yields of tertiary homoallylic alcohols ( 5 – 12 ), which are diastereomerically enriched up to 98%. Configurational assignment by degradation of two of the products to olefins 15 and 18 - through β-hydroxy acids 13 and 16 and β-lactones 14 and 17 - leads to the proposal of a general mechanism and of a specification of the relative topicity lk of the process (Scheme 5). The allylic Ti-compounds 2 can serve as d²-reagents (see the d²-synthon II and the aldol-type structures 1 ).