138571-38-7

Upstream product

• 37466-41-4 3-Hydroxy-4-methoxy-L-phenylalanine methyl ester 
• 138571-42-3 N-BOC-N-methyl-4-iodo-L-phenylalanine 
• 103882-09-3 N-Boc-4-I-Phe-OH 
• 79677-60-4 3-acetyl-O-methyl-N-<(phenylmethoxy)carbonyl>-L-tyrosine methyl ester 
• 132513-32-7 3-hydroxy-O-methyl-N-<(phenylmethoxy)carbonyl>-L-tyrosine methyl ester 

Downstream Products

• 138571-41-2 (9S,12S)-12-{(S)-2-[(S)-2-{[(S)-2-((R)-2-Amino-propionylamino)-propionyl]-methyl-amino}-3-(4-methoxy-phenyl)-propionylamino]-propionylamino}-4-methoxy-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1⁽¹⁷⁾,3⁽¹⁹⁾,4,6,14⁽¹⁸⁾,15-hexaene-9-carboxylic acid; hydrochloride 
• 138605-23-9 BOC-D-alanyl-L-alanyl-N,O⁴-dimethyl-L-tyrosyl-L-alanyl-L-tyrosyl-O⁴-methyl-L-tyrosine cyclic 5⁴<*>6³ ether, methyl ester 
• 138571-40-1 C₄₄H₅₆N₆O₁₂ 
• 138571-36-5 N¹⁵,N²⁹-desmethyl RA-VII 
• 138605-23-9 BOC-D-alanyl-L-alanyl-N,O-dimethyl-L-tyrosyl-L-alanyl-N-methyl-L-tyrosyl-O-methyl-L-tyrosine cyclic 5⁴<*>6³ ether, methyl ester 
• 138571-40-1 C₄₅H₅₈N₆O₁₂ 

Relevant academic research and scientific papers

Total synthesis of cycloisodityrosine, RA-VII, deoxybouvardin, and N29-desmethyl-RA-VII: Identification of the pharmacophore and reversal of the subunit functional roles

Full details of a concise total synthesis of RA-VII (1) and deoxybouvardin (2) are described based on the implementation of an effective intramolecular Ullmann reaction as the key macrocyclization reaction in the preparation of the elusive 14-membered cycloisodityrosine subunit (33) of the bicyclic hexapeptides. Subsequent coupling of 34 to tetrapeptide 17 and macrocyclization with C2-N3 amide bond formation provided 1 and 2. In efforts that address the key structural and conformational features of the agents that contribute to their antitumor activity, N29-desmethyl-RA-VII was prepared and its chemical, conformational, and preliminary biological properties are detailed. The comparable conformational features of N29-desmethyl-RA-VII and RA-VII including a characteristic cis C30-N29 amide bond suggest that the tetrapeptide housed within the 18-membered ring induces the 14-membered cycloisodityrosine to adopt a conformation possessing an inherently disfavored cis secondary or tertiary amide. Moreover, in contrast to prior suppositions in which the rigid 14-membered ring of N-methylcycloisodityrosine has been suggested to serve the functional role of inducing a rigid, normally inaccessible conformation within the biologically relevant D-Ala-Ala-N-Me-Tyr-(OMe)-Ala tetrapeptide, experimental studies demonstrating that the intrinsic activity of the agents resides within the cycloisodityrosine subunit are presented. Thus, the results of the experimental studies require a reversal of the functional roles of the subunits of the agents in which it is the tetrapeptide housed within the 18-membered ring that potentiates the inherent biological properties and alters the conformation of cycloisodityrosine.