130008-93-4

Basic information

• Product Name: cyclo--5-methylheptanoyl>oxy-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> hydrochloride
• Synonyms: cyclo--5-methylheptanoyl>oxy-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> hydrochloride
• CAS NO: 130008-93-4
• Molecular Weight: 852.466
• Mol File: 130008-93-4.mol

Chemical Properties

• CAS DataBase Reference: cyclo--5-methylheptanoyl>oxy-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: cyclo--5-methylheptanoyl>oxy-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> hydrochloride(130008-93-4)
• EPA Substance Registry System: cyclo--5-methylheptanoyl>oxy-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> hydrochloride(130008-93-4)

Safety Data

• Hazardous Substances Data: 130008-93-4(Hazardous Substances Data)

Upstream product

• 129942-53-6 C₅₆H₉₅N₅O₁₃Si 
• 129942-52-5 C₅₆H₉₃N₅O₁₃Si 
• 118878-60-7 (3S,4R)-4-Amino-3-hydroxy-5-methyl-heptanoic acid (S)-1-isopropyl-3-[(S)-3-methyl-1-(2,2,2-trichloro-ethoxycarbonyl)-butylcarbamoyl]-2-oxo-butyl ester 
• 118878-63-0 Z-Thr(Boc-Pro-MeTyr(Me))-Ist-Hip-Leu-OTCE 
• 148914-67-4 C₅₅H₈₁N₅O₁₆ 
• 135103-24-1 Z-Thr(Boc-Pro-MeTyr(Me))-OPE 
• 135103-28-5 Z-Thr(H-MeTyr(Me))-OPE hydrochloride 
• 135214-04-9 H-(3S,4R,5S)-Ist-(2RS,4S)-Hip-Leu-OTCE*HCl 
• 135103-22-9 Z-Thr(Boc-MeTyr(Me))-OPE 
• 135103-21-8 Boc-(3S,4R,5S)-Ist(TBDMS)-(2RS,4S)-Hip-Leu-OTCE 
• 135103-19-4 dibenzyl (S)-⁽³⁾-chloroacetoxy-1,4-dimethyl-2-oxopentane-1,1-dicarboxylate 
• 135103-26-3 Boc-(3S,4R,5S)-Ist-(TBDMS)-OTBDMS 
• 118878-59-4 H-(2RS,4S)-Hip-Leu-OTCE 
• 110720-45-1 N-Boc-O-tert-butyldimethylsilyl-(3S,4R,5S)-isostatine 

Downstream Products

• 110720-12-2 N-Z-didemnin A 
• 312699-33-5 C₅₉H₉₁N₇O₁₅ 
• 161708-52-7 C₆₂H₈₉N₇O₁₅ 
• 161708-48-1 C₆₂H₉₁N₇O₁₆ 
• 77327-04-9 Didemnin A 
• 120286-05-7 Cyclo<(N-L-prolyl-N-methyl-D-leucyl)-O-<oxy>-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> 
• 120286-09-1 Z-didemnin C 
• 120286-08-0 Z-didemnin B 
• 114607-50-0 didemnin B 
• 77327-06-1 didemnin C 

Relevant articles and documents

Synthesis of new didemnin B analogs for investigations of structure/biological activity relationships

Modifications were introduced in the side chain of didemnin B to afford several analogs (1f-1j) for biological testing in order to identify the features responsible for the bioactivity of the natural products (1a-1c). To achieve our goal, two changes were made in the proline ring of the b-turn side chain. Initially, a hydroxyl group was incorporated at the C-4 position of the ring to increase the polar nature of the molecule. Secondly, unsaturation was introduced at C-3 and C-4 to increase the rigidity of the ring and to provide a site for tritiation to follow the drug pathway in biological systems. Improvements were also introduced in the macrocycle construction to produce gram quantities of this unit (1d) for the preparation of the planned analogs. The linear precursor to the macrocycle was oxidized more effectively with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent), and cyclization yields were increased substantially by using a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP). (1H-1,2,3-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and pentafluorophenyl trifluoroacetate were also used to improve other coupling reactions.

Total synthesis of the didemnins; IV. Synthesis of the peptolide ring and construction of the side chain

A total synthesis of didemnins A, B, and C (1-3) which enables these highly cytotoxic cyclopeptides to be prepared in decigram amounts is described. The β-keto acid unit (hydroxyisovaleryl)propionic acid derivative (Hip, 6) was prepared by acylation of dibenzyl methylmalonate and subsequent cleavage of the benzyl groups by the action of boron trichloride. The free β-keto acid 6 was activated by the DCC method and allowed to react with the leucine ester 7 to furnish the amide 8. Activation, deprotection, and ring closure of the linear peptide 19 by means of the pentafluorophenyl ester method in a two-phase system gave rise to the didemnin ring skeleton in 75% yield within a few minutes. The respective side chains were then attached to the didemnin ring easily and in high yields by activation of Z-(R)-N-methylleucine as its 3-cyano-2-pyridylthiol ester followed by reaction with Z-lactylproline chloride and Z-lactic acid chloride.

SYNTHETIC STUDIES OF DIDEMNINS. IV. SYNTHESIS OF THE MACROCYCLE

A stereocontrolled route to the 23-membered macrocycle found in the didemnins is described.