321983-71-5

Basic information

• Product Name: hept-6-en-1-oyl-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid hex-5-enyl ester
• Synonyms: hept-6-en-1-oyl-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid hex-5-enyl ester
• CAS NO: 321983-71-5
• Molecular Weight: 568.757
• Mol File: 321983-71-5.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: hept-6-en-1-oyl-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid hex-5-enyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: hept-6-en-1-oyl-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid hex-5-enyl ester(321983-71-5)
• EPA Substance Registry System: hept-6-en-1-oyl-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid hex-5-enyl ester(321983-71-5)

Safety Data

• Hazardous Substances Data: 321983-71-5(Hazardous Substances Data)

Upstream product

• 247186-15-8 (tert-butoxycarbonyl)-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid methyl ester 
• 222556-21-0 (S)-tetrahydro-pyridazine-1,2,3-tricarboxylic acid 1,2-di-tert-butyl ester 3-methyl ester 
• 13734-41-3 t-Boc-L-valine 
• 247186-17-0 hept-6-en-oyl-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic acid methyl ester 
• 247186-16-9 (tert-butoxycarbonyl)-L-valine-L-phenylalanine-hexahydropyridazine-3S-carboxylic asid methyl ester 
• 1119-60-4 hept-6-enoic acid 
• 821-41-0 5-Hexen-1-ol 
• 138323-07-6 methyl (S)-hexahydropyridazine-3-carboxylate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Downstream Products

• 321983-72-6 (E)-(3S,6S,21S)-3-benzyl-6-isopropyl-19-oxa-1,4,7,25-tetraaza-bicyclo[19.3.1]-pentacos-13-ene-2,5,8,20-tetraone 

Relevant articles and documents

Sanglifehrin-cyclophilin interaction: Degradation work, synthetic macrocyclic analogues, x-ray crystal structure, and binding data

Sanglifehrin A (SFA) is a novel immunosuppressive natural product isolated from Streptomyces sp. A92-308110. SFA has a very strong affinity for cyclophilin A (IC50 = 6.9 ± 0.9 nM) but is structurally different from cyclosporin A (CsA) and exerts its immunosuppressive activity via a novel mechanism. SFA has a complex molecular structure consisting of a 22-membered macrocycle, bearing in position 23 a nine-carbon tether terminated by a highly substituted spirobicyclic moiety. Selective oxidative cleavage of the C26 = C27 exocyclic double bond affords the spirolactam containing fragment 1 and macrolide 2. The affinity of 2 for cyclophilin (IC50 = 29 ± 2.1 nM) is essentially identical to SFA, which indicates that the interaction between SFA and cyclophilin A is mediated exclusively by the macrocyclic portion of the molecule. This observation was confirmed by the x-ray crystal structure resolved at 2.1 A of cyclophilin A complexed to macrolide 16, a close analogue of 2. The x-ray crystal structure showed that macrolide 16 binds to the same deep hydrophobic pocket of cyclophilin A as CsA. Additional valuable details of the structure-activity relationship were obtained by two different chemical approaches: (1) degradation work on macrolide 2 or (2) synthesis of a library of macrolide analogues using the ring-closing metathesis reaction as the key step. Altogether, it appears that the complex macrocyclic fragment of SFA is a highly optimized combination of multiple functionalities including an (E,E)-diene, a short polypropionate fragment, and an unusual tripeptide unit, which together provide an extremely strong affinity for cyclophilin A.