Cube-octameric silsesquioxane (POSS) based conjugation scaffolds for copper catalysed azide-alkyne [3+2] cycloaddition are reported. The synthetic route to octaazido and octaalkyno functionalised POSS templates without cage rearrangements is described. A set of click couplings is conducted including the first effective conjugation with a fully unprotected functional peptide towards a POSS assembled peptide octamer.

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The absolute configuration of 1,2‐diols formed by a primary and a secondary (chiral) hydroxyl group can be deduced by comparison of the 1H NMR spectra of the corresponding (R)‐ and bis‐(S)‐MPA esters (MPA=methoxyphenylacetic acid). This method involves the use of the chemical shifts of substituents L1/L2 attached to the secondary (chiral) carbon, and of the hydrogen atom linked to the chiral center (CαH) as diagnostic signals. Theoretical (AM1, HF, and B3 LYP calculations) and experimental data (dynamic and low‐temperature NMR spectroscopy, studies on deuterated derivatives, constant coupling analysis, circular dichroism (CD) spectra, and NMR studies with a number of diols of known absolute configuration) prove that the signs of the ΔδRS obtained for those signals correlate with the absolute configuration of the diol. A graphical model for the reliable assignment of the absolute configuration of a 1,2‐diol by comparison of the NMR spectra of its bis‐(R)‐ and bis‐(S)‐MPA esters is presented.

We have evaluated different strategies for the one-pot synthesis of D-fructose 6-phosphate and its 1-deoxy and 3-deoxy analogs from readily available starting materials, by building up ''artificial metabolisms'' in vitro. The first consisted of an aldol cleavage-aldol formation cascade, in which glyceraldehyde 3-phosphate as the central intermediate is generated from fructose 1,6-bisphosphate and consumed in situ for a consecutive carboligation step catalyzed by fructose 6-phosphate aldolase (FSA). The second approach consisted of an aldolase-kinase coupling, in which the unphosphorylated ketose was produced in situ by FSA-catalyzed carboligation, followed by a hexokinase-catalyzed phosphorylation step. While both approaches profited from the high stereoselectivity and stability of the aldolases used, the first approach proved to be the most practical, effective and economical, whereas the second strongly depends on the substrate specificity of hexokinase, which shows inferior catalytic efficiency with the 1-deoxy substrate. Phosphorylation of 3-deoxyfructose failed because, contradictory to a literature report, this compound was found not to be acceptable as a substrate of yeast hexokinase.

A convenient, rapid and widely applicable one-pot procedure has been developed for the synthesis of acetylenedicarboxamides from various primary and secondary amines, including amino acid derivatives, protected carbohydrates, and fluorescent labels. By using DMTMM for amide coupling, acetylenedicarboxylic acid was directly converted into acetylenedicarboxamides in highly competitive overall yields (52-80%).Acetylenedicarboxylic acid (ADA, 1) and its derivatives are widely used compounds in the synthesis of carbo-and heterocycles. In the case of acetylenedicarboxylic acid diesters the electron-deficient triple bond readily reacts as a dipolarophile or dienophile in thermal cycloadditions, and as a conjugate acceptor in Michael additions. 1 Often, both types of reaction pathways are involved in the synthesis of heterocyclic systems when using ADA derivatives. 2 As part of our ongoing research on the multidecoration of nanoscaffolds by 'click'-type conjugation reactions, 3 in particular by using ADA diesters as both functionalizing and branching elements, 3a we were interested in acetylenedicarboxylic diamides (ADCAs) as chemically more stable analogues of diesters. However, the formation of amides of ADA 1 suffers from competing and/or subsequent Michael additions of the amine component because of the highly electrophilic nature of the conjugated triple bond. Only a few general protocols for the preparation of ADCAs have been described (Scheme 1) that are based on acid halides such as dibromofumaroyl dichloride (2) 4 or acetylenedicarbonyl difluoride (3). 5 Reports on the use of acetylenedicarbonyl dichloride (4) remain controversial, 6 with only few applications for the synthesis of ADCAs; 7 mixed anhydrides of 1 tend to polymerize. 8 All these protocols require several steps and involve sensitive reagents or intermediates. The widely applied standard technique for direct amide coupling using carbodiimides seems to be generally inefficient in the case of 1, 9 and our attempts to prepare ADCAs via carbonyldiimidazole activation 10 also resulted in no product formation.On the assumption that ADA deprotonation should render the triple bond more electron rich 11 and hence more stable to conjugate nucleophilic attack by amines, we, therefore, searched for a coupling reagent that involves the incipient formation of an ionic ammoniumcarboxylate intermediate in the reaction mechanism.Scheme 1 Common strategies for the synthesis of acetylenedicarboxamides: Reagents and conditions: (i) Br 2 ; (ii) PCl 5 ; (iii) R 1 NHR 2 ; (iv) Zn; (v) SF 4 (X = F) or SOCl 2 (X = Cl).From the broad range of peptide-coupling reagents 12 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 5), 13 which is commercially available or can be readily prepared from cyanuric chloride in two steps, 14,15 seemed to be a reagent that could fulfill this condition. Indeed, when using a slightly modified Kunishima protocol 15 for a test reaction of 1 with 2-phenylethylamine (6a) in tetrahydrofuran the desired N 1 ,N 4 -diphenethylbut...