A Modular Synthesis of Teraryl-Based α-Helix Mimetics, Part†4: Core Fragments with Two Halide Leaving Groups Featuring Side Chains of Proteinogenic Amino Acids.

Teraryl-based α-helix mimetics have proven to be useful compounds for the inhibition of protein-protein interactions (PPI). We have developed a modular and flexible approach for the synthesis of teraryl-based α-helix mimetics using a benzene core unit featuring two halide leaving groups of differentiated reactivity in the Pd-catalyzed cross-coupling used for teraryl assembly. The use of para-bromo iodoarene core fragments resolved the issue of hydrolysis during cross-coupling that was observed when using triflate as a leaving group. We report a complete set of para-bromoiodoarene core fragments decorated with side chains of all proteinogenic amino acids relevant for PPI (Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val). In order to be compatible with general cross-coupling conditions, some of the nucleophilic side chains had to be provided in a protected form to serve as stable building blocks.

After chemo-metamorphosis: p-menthane monoterpenoids characterize the oil gland secretion of adults of the oribatid mite, Nothrus palustris.

The oil gland secretion of the oribatid mite Nothrus palustris is known to show the phenomenon of juvenile-adult polymorphism, i.e., juvenile instars produce secretions predominated by geranial, whereas adults secrete dehydrocineole along with a number of chemically unidentified compounds. We here re-analyzed the secretions of adult N. palustris by GC-MS and NMR spectroscopy, eventually identifying the unknown compounds as p-menthane monoterpenoids. The major components were two isomeric 6-isopropenyl-3-methyl-cyclohex-3-en-1-yl formates (= p-1,8-menthadien-5-yl formates), which accounted for about 75% of the secretion. These were accompanied by five additional, only partly identified p-menthanes (or p-methane-derivatives), all of which represented minor or trace components. In addition, adult secretions contained two C21-hydrocarbons, 1,12-heneicosadiene (major) and a heneicosatriene (minor). Menthane monoterpenoids represent a novel sub-class of terpene compounds in the oil gland secretions of Oribatida. In case of N. palustris, we assume that both geranial and p-menthane monoterpenoids arise via the mevalonate pathway which obviously shows a split at the level of geranyl pyrophosphate, leading to geranial in juveniles and to p-menthanes in adults. The significance of methane occurrence in oil glands as well as the taxonomic distribution of juvenile-adult polymorphism in oribatid oil gland secretions is discussed. The latter phenomenon-i.e., "chemo-metamorphosis" of secretions-is not known from early- and middle-derivative Oribatida nor from Astigmata, but appears to be more common in some derivative desmonomatan and brachypyline oribatid groups.

The scent gland chemistry of Gagrellinae (Opiliones, Sclerosomatidae): evidence for sequestration of myrmicacin in a species of Prionostemma.

The scent gland secretion of an undetermined species of Prionostemma from Costa Rica was analyzed by gas chromatography-mass spectrometry and shown to consist of medium-chain carboxylic acids (mainly octanoic acid) and a ß-hydroxy-carboxylic acid, eventually identified as myrmicacin (= (R)-3-hydroxydecanoic acid). While scent gland secretions in harvestmen have traditionally been considered to be products of de novo synthesis, we here provide evidence for the unusual case of sequestration-derived scent gland constituents: at least myrmicacin appears to be sequestered from leaf-cutter ants that constitute a part of the prey of the Prionostemma-species herein investigated. This is the first report on the scent gland chemistry of the sclerosomatid subfamily Gagrellinae as well as on a possible sequestration mechanism in harvestmen.

Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids.

We report the synthesis of diverse ß-hydroxy-α,α-dialkyl-α-amino acids with perfect stereoselectivity for the α-quaternary center through the action of l- and d-specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 % were obtained. In the case of d-selective threonine aldolase from Pseudomonas sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d-threonine aldolase from Pseudomonas sp., (2R,3S)-2-amino-3-(2-fluorophenyl)-3-hydroxy-2-methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the syn-product. A Birch-type reduction enabled the reductive removal of the ß-hydroxy group from (2S)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-α-methyl-phenylalanine via a two-step chemo-enzymatic transformation.