104324-22-3Relevant academic research and scientific papers
Total synthesis of bleomycin A2 and related agents. 1. Synthesis and DNA binding properties of the extended C-terminus: Tripeptide S, tetrapeptide S, pentapeptide S, and related agents
Boger, Dale L.,Colletti, Steven L.,Honda, Takeshi,Menezes, Royce F.
, p. 5607 - 5618 (2007/10/02)
Full details of concise, diastereocontrolled syntheses of 2-5 and their incorporation into tri-, tetra-, and pentapeptide S, the C-terminus of bleomycin A2, are described. The extension of the studies to the synthesis of a complete set of tri- and tetrapeptide S structural analogs 29a,b and 43b-j is detailed, and their DNA binding constants (apparent K(B), calf thymus DNA) and apparent binding site sizes were determined. Consistent with past observations, the studies highlight the fact that the majority of the DNA binding affinity for bleomycin A2 (1.0 X 105 M-1) and deglycobleomycin A2 (1.1 x 105 M-1) is embodied within N-BOC-tripeptide S (0.26 x 105 M-1). The additional comparisons of 29a (0.18 x 105 M-1), N-BOC-tetrapeptide S (0.21 x 105 M-1), 43h (0.20 x 105 M-1), and N-BOC pentapeptide S (0.23 x 105 M-1) versus N-BOC-dipeptide S (0.10 x 105 M-1) indicate productive stabilizing binding interactions for the tripeptide S L-threonine subunit and substituent, illustrate that the entire pentanoic acid subunit of tetrapeptide S and its substituents do not significantly contribute to DNA binding affinity, and indicate that the entire β-hydroxy-L-histidine subunit of pentapeptides does not contribute to DNA binding affinity. With the exception of the L-threonine side chain substituent, the observations suggest that the tri- and tetrapeptide S substituent effects on the bleomycin A2 DNA cleavage reaction are not due to substantial stabilizing binding interactions with duplex DNA. In addition, the measured apparent binding site sizes for bleomycin A2 (3.8 base pairs), deglycobleomycin A2 (3.9 base pairs), N-BOC-tripeptide S (3.6 base pairs), N-BOC-tetrapeptide S (3.7 base pairs), 43h (3.5 base pairs), and N-BOC-pentapeptides (4.2 base pairs) versus N-BOC-dipeptide S (2.2 base pairs) and 29a (2.7 base pairs) suggest that it is the tripeptide S subunit of bleomycin A2 that is fully bound to duplex DNA, that the tripeptide S L-threonine hydroxyethyl substituent detectably affects the agent interaction with duplex DNA, but that the presence or absence of the other tetrapeptide S and pentapeptide S backbone substituents do not substantially alter the binding site size or tripeptide S binding mode.
Synthesis of Tri- and Tetrapeptide S: The Extended C-Terminus of Bleomycin A2
Boger, Dale L.,Menezes, Royce F.
, p. 4331 - 4333 (2007/10/02)
Concise diastereocontrolled syntheses of tri- and tetrapeptide S, key subunits of the antitumor antibiotic bleomycin A2, are detailed.
Asymmetric Glycine Enolate Aldol Reactions: Synthesis of Cyclosporine's Unusual Amino Acid, MeBmt
Evans, David A.,Weber, Ann E.
, p. 6757 - 6761 (2007/10/02)
The chiral glycine synthon, 3c, as its derived stannous enolate, has been demonstrated to undergo a highly syn diastereoselective aldol addition reaction with representative aldehydes to give the adducts 5 (R = C6H5, Me, Me2CH) in yields ranging from 71 to 92percent.The utility of these intermediates has been demonstrated via the subsequent three-step transformation of these adducts to the enantiomerically pure N-methyl β-hydroxy amino acids 1.This reaction methodology has been applied to the asymmetric synthesis of (4R)-4-((E)-2-butenyl)-4,N-dimethyl-L-threonine (1a), an important constituent in the immunosuppressant peptide cyclosporine.Several additional structural analogues of 1a were also prepared in conjunction with this study.
