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New total synthesis of dendroamide a from dehydrodi- and tripeptides

New total synthesis of triheterocyclic cyclopeptide bistratamide-type dendroamide A, isolated from the cyanobacterium Stigonema dendroideum, was achieved by various conversions of Delta1-dehydrodi- and Delta3-dehydrotripeptides.

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METHOD FOR PREPARING COMBRETASTATIN

The Invention relates to a method for preparing a combretastatin (A): formula (I) in the form of a base or of an addition salt with an acid, which comprises coupling, in the presence of a base and of T3P, the salt of the (Z)-amino compound of formula (II) with a doubly protected L-serine derivative of formula (III) in which PG denotes a group protecting the amine function, so as to obtain the compound of formula (Z)-(Ib): formula (IV), then deprotecting and opening the ring of (Z)-(Ib) in the presence of an acid, so as to obtain the combretastatin (A) in the form of a salt; and, optionally, adding a base, so as to obtain the combretastatin (A) in the form of a base, the salt of the (Z)-amino compound having been obtained by enrichment of the salt of the amino compound of formula (V) in (Z) isomer.

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Synthesis of D-erythro-sphingosine and D-erythro sphinganine via 3- ketosphinganine

D-erythro- sphingosine and D-erythro-sphinganine can be produced in protected form from serine by a synthetic approach in which the normal biological intermediate 3-ketosphinganine in protectyed form, is a key synthetic intermediate. The sequence is short and convergent, proceeds in good overall yields (? 30% for 6 steps) and with excellent stereocontrol (>91% de, >95% ee).

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Total synthesis of (-)-ulapualide A: The danger of overdependence on NMR spectroscopy in assignment of stereochemistry

Lessons learnt: The asymmetric total synthesis of the macrolide (-)-ulapualide A has been accomplished. Interestingly, the 1H NMR spectrum and chiroptical data of the macrolide and of a previously synthesized diastereoisomer with opposite stereocenters at C3, C28, C29, C30, and C32 were superimposable, which highlights the care that must be taken in the assignment of configurations to complex structures based on NMR spectroscopy. (Chemical Equation Presented)

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SUBSTITUTED ISOQUINOLINES AND THEIR USE AS TUBULIN POLYMERIZATION INHIBITORS

The present invention relates generally to substituted isoquinolines and their use as tubulin polymerization inhibitors. In particular, the invention relates to substituted isoquinolines which possess useful therapeutic activity, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds

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Diastereoselective Passerini reaction of chiral 2,3-epoxy aldehydes with TosMIC

A diastereoselective three-component Passerini reaction (P-3CR) of chiral 2,3-epoxy aldehydes with tosylmethyl isocyanide (TosMIC) under benzoic acid conditions to afford densely substituted products in moderate to good yields and diastereomeric excess is reported. Georg Thieme Verlag Stuttgart.

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COMBRETASTATIN DERIVATIVE PREPARATION METHOD

The invention relates to a method for preparing a combretastatin derivative (I) or (II), said method including the following steps: triaryl(3,4,5-trimethoxybenzyl)phosphonium halide P3 (III), wherein Ar denotes an aryl group selected from among phenyl or thienyl, is reacted with P2 having formula (IV) or P?2 having formula (V) so as to respectively obtain the compound P4 or P?4, which have formulas (VI) and (VII), respectively; then, during a step for deprotection in the presence of an acid and/or a base, the compound having P4 or P?4 leads, after an optional purification step, to the compound having formula (I) or (II).

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A reasonably stereospecific multistep conversion of Boc-protected alpha-amino acids to Phth-protected beta3-amino acids

A method for the synthesis of beta3-amino acids starting from alpha-amino acids is described. This conversion can be effected by an eight-step procedure which involves the transformation of the carboxylic group into an alkyne followed by a selenium-mediated conversion of the carbon-carbon triple bond to a Se-phenyl selenocarboxylate intermediate. The reactive Se-phenyl selenocarboxylate intermediates can be trapped with water, alcohols or the amine of an amino acid derivative to give beta3-amino acids, beta3-amino esters or mixed peptides, respectively. The whole transformations of the carboxylic group into an alkyne and of the alkyne group into beta3-amino acids may not require purification of the intermediate products but a work-up and isolation procedure of crude materials.

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Enantiopure N-protected alpha-amino glyoxals 1. Synthesis from alpha-amino acids and some condensation reactions with amines

A series of N-protected alpha-ammo diazoketones has been prepared from L-amino acids and dipeptides and used as precursors in the synthesis of novel N-protected alpha-amino glyoxals via oxidation with distilled dimethyldioxirane (DMD) in acetone. The glyoxals have been converted, without purification, into enantiopure imines, pyrazines, quinoxalines, and pyrido[2,3-b]pyrazines via condensation with the appropriate amine or diamine. The molecular structure of the pyrido[2,3-b]pyrazine derived from N-Cbz-L-phenylalanine has been determined by X-ray analysis.

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Facile and efficient addition of terminal alkynes to benzotriazole esters: Synthesis of d-erythro-sphingosine using ynones as the key intermediate

From the perspective of synthesis, ynones are compounds of considerable interest because of their occurrence in a wide variety of biologically active molecules and as key synthetic intermediates. In this context, a facile and highly efficient synthesis of ynones was developed based on the high reactivity of benzotriazole esters formed in situ. Lithium acetylides can alkylate various carboxylic acids in yields ranging from 60% to 92%. To determine whether our methodology is useful for synthesising complex and biologically relevant molecules, we synthesise d-erythro-sphingosine in four steps and with 33% overall yield from l-serine.

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