Synthesis of cryptophycins via an N-acyl-beta-lactam macrolactonization

An efficient and concise approach to the synthesis of the macrolide core of the cryptophycins has been developed. A novel macrolactonization utilizing a reactive acyl-beta-lactam intermediate incorporates the beta-amino acid moiety within the 16-membered macrolide core. This modular approach, involving a cyanide-initiated acyl-beta-lactam ring opening followed by cyclization, was successfully applied to the total synthesis of cryptophycin-24. The strategy was also used in an efficient synthesis of the 6,6-dimethyl-substituted dechlorocryptophycin-52. In this case, the cyanide-initiated ring opening of the bis-substituted 2-azetidinone followed by macrolactonization was achieved through a catalytic process.     

Thermal synthesis of the optical pure pentapeptide derivative Z-(L)-Ala-(L)-Phe-Gly-(L)-Phe-Gly-OMe

The pentapeptide Z-(L)-Ala-(L)-Phe-Gly-(L)-Phe-Gly-OMe was obtained by reacting the activated dipeptide derivative Z-(L)-Ala-(L)-Phe-OPcp with the amino peptide derivative TFA·H-Gly-(L)-Phe-Gly-OMe at 100–105°C under reduced pressure (10^?2-10-^?3 Torr) without using solvents. The product obtained by bulk condensation showed no racemization, whereas the product obtained by a matrix mediated condensation contained 5,5 % diastereomer Z-(L)-Ala-(D)-Phe-Gly-(L)-Phe-Gly-OMe. Separation of diastereomers was achieved by HPLC on a silicagel column.     

The Radical Anions of N,N′-Dicyanoquinone Diimines,a New Class of Electron Acceptors

The radical anions of 12 N,N′-dicyanoquinone diimines, a new class of electron acceptors, hace been characterized by their hyperfine data with the use of ESR and ENDOR spectroscopy. The largest coupling constant (0.30–0.45 mT), due to the two ¹⁴N nuclei in the exocyclic positions, gives rise to a conspicuous broadening of the peripheral ESR lines by an incomplete averaging of the hyperfine anisotropy. The most plausible interpretation of the experimental results for the radical anions of N,N′-dicyano- 1,4-benzoquinone diimine ( 1 ) and N,N′-Dicyano-9,10-anthraquinone diimine ( 9 ) is in terms of both ‘syn’- and ‘anti’-configurations contributing to the ESR and ENDOR spectra and having equal proton- and ¹⁴N-coupling constants. The π-spin distribution in the radical anions of N,N′-dicyanoquinone diimines is compared with those in the analogous ions of tetracyanoquinodimethanes and quinones.     

MUTATIONS IN SACCHAROMYCES CEREVISIAE AFFECTING SENSITIVITY TO PHOTODYNAMIC INACTIVATION

Abstract— Mutants of Saccharomyces cerevisiae with varying photodynamic sensitivities were isolated in an attempt to help identify the cytoplasmic targets of photodynamic action in yeast.     

Solid-phase synthesis of metal-complex containing peptides

We report the synthesis of Fmoc protected single amino acid chelates (SAAC) and their metal complexes. The modified amino acids are suitable for solid-phase peptide synthesis. The use of 4-hydroxymethylbenzoic acid AM (HMBA-AM) resin allows the nucleophilic cleavage of the peptide-metal complexes from the resin without decomplexation.     

Phospholipid mesophases at solid interfaces: in-situ X-ray diffraction and spin-label studies

In this work, we report on recent investigations, both on the global and on the local molecular architecture of supported phospholipid model membranes. A brief theoretical introduction explains how global structural information on supramolecular lipid ensembles can be retrieved from surface X-ray diffraction measurements as well as how spin-label electron paramagnetic resonance spectroscopy (EPR) provides complementary information on the local environment of probe molecules. The combination of especially designed X-ray cells with the technique of small- and wide-angle X-ray surface scattering makes it possible to explore various fields of lipid research and its applications. Examples for different physico-chemical conditions are presented: (i) in situ chemistry under excess of water conditions demonstrating how solid-supported lipid films sense salinity, (ii) the 3D electron density reconstruction of a vesicle-fusion intermediate under controlled humidity, and (iii) complementary temperature and pressure effects on oriented phospholipid samples. Further, special attention has been given to the influence of different film preparation techniques with respect to quality and the defect structure manifestation. To resolve the proportions and local properties of defects in a hydrated lipid-deposited surface, spin-label EPR was applied. The results from 9.6 GHz EPR as well as from 1.2 GHz EPR suggest the alignment to be in the range between 30% and 80%. In addition, slow time-dependent EPR measurements point to nano-structural rearrangements due to water flow and reduction of alignment quality.     

Chain-length dependence of the conformational order in self-assembled dialkylammonium monolayers on mica studied with soft X-ray absorption

Self-assembled alkyl chain based monolayers on mica are important for industrial and technological processes since they can be employed for an organic modification of the inorganic substrate. The conformational structure and orientational order of the films determine the interaction of the modified substrate with the environment and the chemical character and stability of its surface. We have studied the conformational order in ion exchanged dialkylammonium monolayers adsorbed on mica depending on the length of the alkyl chains systematically with near-edge X-ray absorption fine structure spectroscopy (NEXAFS). In addition, films were characterized by water contact angle measurements. The experimentally determined average tilt angles of the chains are discussed in terms of the degree of order. It was found that the absolute number of gauche defects in the films increases with decreasing chain length.