Synthesis of the alkaloid homaline in ( ) and natural (S,S)-(-) forms, using amination and transamidative ring expansion in liquid ammonia.

Crombie, Leslie; Haigh, David; Jones, Raymond C. F.; Mat-Zin, A.Rasid. Dep. Chem., Univ. Nottingham, Nottingham, UK. Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1993), (17), 2047-54. CODEN: JCPRB4 ISSN: 0300-922X. Journal written in English. CAN 120:164608 AN 1994:164608 CAPLUS (Copyright (C) 2009 ACS on SciFinder (R)) Abstract The alkaloid homaline I was prepd. in (?) and natural (S,S)-(-) forms. Linking of 2-azacyclooctanone units either directly or successively using 1,4-dihalogenobutanes or 1,4-dihalogenobut-2-ynes is examd. (?)-5-Methyl-4-phenyl-1,5-diazacyclooctan-2-one is first made by a 2,2'-dithiodipyridine/triphenylphosphine-mediated cyclization, and then by amination and transamidative ring expansion from N-(3-chloropropyl)-4-phenylazetidin-2-one in liq. ammonia, followed by N-methylation. Coupling through a 1,4-dihalogenobutane of either the N-methylated azalactam, or the unmethylated azalactam followed by methylation, gave homaline in (?) and meso forms. (R)-(-)-phenylglycine was converted via (S)-?-phenyl-?-alanine into an (S)-?-lactam which was then alkylated with 1-bromo-3-chloropropane, and aminated and ring expanded in liq. ammonia. Coupling of the homochiral azalactam (2 mol) so formed with 1,4-dibromobutane, followed by N-methylation, gave (S,S)-(-)-homaline identical with the natural material.

Study of the transamidative ring expansion of N--halogenoalkyl--lactams of alkyl chain lengths 2–12 in liquid ammonia and other liquid amines: syntheses of 7-, 8- and 9-membered 1,5-diaza cyclic ketones, including routes to (±)-dihydroperiphylline and (±)-celabenzine

N-(3-Halogenopropyl)-4-phenylazetidin-2-ones undergo amination in liquid ammonia followed by transamidative ring expansion to give the eight-membered 4-phenyl -1,5-diazacyclooctan-2-one in excellent yield. Ring expansion of the amines in liquid ammonia is found to be much more effective than in hydrocarbon solvents. Formation of 7-, 8-, and 9-membered azalactams from the requisite -halogenoalkyl--lactams is an excellent synthetic process, though it is not applicable to 10membered rings. In the cases of rings of 13-, 15- and 17-members, although amination and apparent expansion takes place, the large rings appear not to be stable to ammonia and the final products are acyclic amides. N-[4-Halogenobut-2(Z)-enyl]-4-phenylazetidin-2-one satisfactorily forms a 9-membered (Z)-olefinic azalactam, but the (E)-isomer gives an acyclic amino amide. By using alkyl-substituted -lactam side-chains, C-substituted medium rings can be obtained; the relative instability of N-acyl -lactams to ammonia, however, leads to acylamino amides rather than expanded rings.Employing ethylamine in place of ammonia, it is shown that N-ethylated azalactams are formed satisfactorily, and using allylamine, N-allyl medium rings capable of further elaboration are obtained. The chemistry of these systems is discussed. Using transamidation in liquid ammonia, a short synthesis of the 9-membered spermidine alkaloid (±)-dihydroperiphylline is reported. Synthesis of key intermediates, whose transformation into the 13-membered alkaloids of the celabenzine group has already been effected, has been carried out.X-Ray single-crystal structure determinations for 4-phenyl-1,5-diazacyclononan-2-one, trans-4-phenyl-8-methyl-1,5-diazacyclooctan-2-one and (Z)-4-phenyl-1,5-diazacyclonon-7-en-2-one are reported, and comment is made on certain conformational features.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009

Temperature dependence of the mid-infrared dielectric function of YBCO in the a-b plane: a re-evaluation

The a-b plane dielectric function (epsilon) of c-axis YBa2Cu3O7-delta thin films with T-c > 85 K was measured at lambda = 3.392 mum in the temperature range 85-300 It, using an attenuated total reflectance (ATR) technique based on the excitation of surface plasmons, The results show that \epsilon (r)\ decreases quasi-linearly with increasing temperature, while Ei is invariant to temperature within experimental uncertainties. Typical values are epsilon (ab) = -23 + 16.5i at similar to 295 R and epsilon (ab) = -27 + 15.5i at similar to 90 K. A generalised Drude analysis yields effective scattering rates (1/tau*) that increase with temperature from similar to 1500 to similar to 1900 cm(-1). The temperature dependent rates best fit an equation of the form 1/tau* = a + bT(alpha) with alpha = 1.46 +/- 0.40. The effective plasma frequencies of w(p)* similar to 18,500 cm(-1) are almost independent of temperature. The uniquely detailed temperature dependence of the results confirm and consolidate data obtained by other groups using normal reflectance methods, but contradict our previously published ATR measurements. Technical shortcomings in the earlier work are identified as the source of the discrepancy. (C) 2000 Elsevier Science B.V. All rights reserved.

Observation of Postsoliton Expansion Following Laser Propagation through an Underdense Plasma

The expansion of electromagnetic postsolitons emerging from the interaction of a 30 ps, 3 x 10(18) W cm(-2) laser pulse with an underdense deuterium plasma has been observed up to 100 ps after the pulse propagation, when large numbers of postsolitons were seen to remain in the plasma. The temporal evolution of the postsolitons has been accurately characterized with a high spatial and temporal resolution. The observed expansion is compared to analytical models and three-dimensional particle-in-cell results, revealing a polarization dependence of the postsoliton dynamics.

Shock creation and particle acceleration driven by plasma expansion into a rarefied medium

The expansion of a dense plasma through a more rarefied ionized medium is a phenomenon of interest in various physics environments ranging from astrophysics to high energy density laser-matter laboratory experiments. Here this situation is modeled via a one-dimensional particle-in-cell simulation; a jump in the plasma density of a factor of 100 is introduced in the middle of an otherwise equally dense electron-proton plasma with an uniform proton and electron temperature of 10 eV and 1 keV, respectively. The diffusion of the dense plasma, through the rarefied one, triggers the onset of different nonlinear phenomena such as a strong ion-acoustic shock wave and a rarefaction wave. Secondary structures are detected, some of which are driven by a drift instability of the rarefaction wave. Efficient proton acceleration occurs ahead of the shock, bringing the maximum proton velocity up to 60 times the initial ion thermal speed. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3469762]