146232-49-7

Upstream product

• 4509-90-4 5-bromovaleroyl chloride 
• 40217-17-2 (R)-4-(phenylmethyl)-2-oxazolidinone 
• 2067-33-6 5-bromopentanoic acid 

Downstream Products

• 146232-50-0 (4R)-3-<(3R)-N,N'-bis(t-butoxycarbonyl)hexahydropyridazine-3-carboxy>-4-phenylmethyl-2-oxazolidinone 
• 1424402-11-8 (S)-6-azido-3-((R)-4-benzyl-2-oxooxazolidine-3-carbonyl)hexanoic acid tert-butyl ester 
• 1424402-08-3 1-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-5-azido-1-pentanone 
• 32655-45-1 (3R)-N¹-(2,4-dinitrophenyl)hexahydropyridazine-3-carboxylic acid 
• 32655-46-2 methyl (3R)-N¹-(2,4-dinitrophenyl)hexahydropyridazine-3-carboxylate 
• 146232-51-1 (3R)-N,N'-bis-(t-butoxycarbonyl)hexahydropyridazine-3-carboxylic acid 
• 174497-79-1 C₂₅H₃₅N₃O₇ 

Relevant academic research and scientific papers

Synthesis of the Bioherbicidal Fungus Metabolite Macrocidin A

The second total synthesis of macrocidin A afforded the bioherbicidal fungal metabolite in 16 steps starting from doubly protected l-tyrosine. The 3-octanoyl side chain with the α-methyl group and an ω-bromo epoxide already in place was attached to the te

Conjugates of modified cryptophycins and RGD-peptides enter target cells by endocytosis

Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized β2-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

Enantioselective synthesis of (3R)- and (3S)-piperazic acids. The comparative unimportance of DMPU mediated retro-hydrazination

In response to a recent literature report by Decicco and Leathers, the work of Hale, Delisser, and Manaviazar (1992) on the asymmetric synthesis of (3R)- and (3S)-piperazic acids has been reinvestigated, and the originally claimed product yields fully substantiated. The claims made in reference 13 about the proportions of cyclised product 6 and starting bromide 20 isolated from the low temperature electrophilic hydrazination-nucleophilic cyclisation of 20 with di-t-butylazodicarboxylate (DBAD) and DMPU as an additive are inaccurate. The retro-hydrazination reaction that they claim is problematic when DMPU is added to the hydrazinated reaction mixture has been demonstrated not to have a seriously detrimental effect on cyclisation product yield and to be unimportant. The other main ion of reference 13, that the electrophilic hydrazination and nucleophilic cyclisation of 20 gives 6 in 91% isolated yield when n-Bu4NI is employed as an additive (instead of DMPU) has also been shown to be in error. We have carefully repeated a scaled-down version of the n-Bu4NI catalysed procedure and have found that 6 is generally isolated in yields of 50-56% after flash chromatography. We have concluded that n-Bu4NI does not significantly increase the yields of cyclisation products 6 or 17 when it is employed as a cyclisation additive. Herein, we report details of our two preferred 'crude' experimental procedures for preparing the enantiomers of piperazic acid in high optical purity, neither of which requires chromatographic purification of the reaction intermediates en route. Both these preferred 'crude' methods for preparing 11 and 19 have been consistently reproduced many times in these laboratories over the past few years. In our view, they remain the most expedient and highest yielding methods currently available for obtaining 11 and 19 in high optical purity.

AZINOTHRICIN SYNTHETIC STUDIES. 1. EFFICIENT ASYMMETRIC SNTHESES OF (3R)- AND (3S)-PIPERAZIC ACIDS

A convenient asymmetric synthesis of both (3R)-and (3S)-piperazic acids has been developed that is based on electrophilic hydrazination of a chiral bromovaleryl carboximide enolate with di-tert-butyl azodicarboxylate, followed by subsequent intramolecular