121054-30-6Relevant articles and documents
Nine enzymes are required for assembly of the pacidamycin group of peptidyl nucleoside antibiotics
Zhang, Wenjun,Ntai, Ioanna,Bolla, Megan L.,Malcolmson, Steven J.,Kahne, Daniel,Kelleher, Neil L.,Walsh, Christopher T.
supporting information; experimental part, p. 5240 - 5243 (2011/06/17)
Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted peptidyl chain with a β-peptide and a ureido linkage as well as a 3′-deoxyuridine nucleoside attached to DABA 3 of the peptidyl chain via an enamide linkage. Although the biosynthetic gene cluster for pacidamycins was identified recently, the assembly line of this group of peptidyl nucleoside antibiotics remained poorly understood because of the highly dissociated nature of the encoded nonribosomal peptide synthetase (NRPS) domains and modules. This work has identified a minimum set of enzymes needed for generation of the pacidamycin scaffold from amino acid and nucleoside monomers, highlighting a freestanding thiolation (T) domain (PacH) as a key carrier component in the peptidyl chain assembly as well as a freestanding condensation (C) domain (PacI) catalyzing the release of the assembled peptide by a nucleoside moiety. On the basis of the substrate promiscuity of this enzymatic assembly line, several pacidamycin analogues were produced using in vitro total biosynthesis.
New synthesis and ring opening of cis-3-alkylaziridine-2-carboxylates
Lee, Kwang-Deuk,Suh, Jang-Min,Park, Jae-Hoon,Ha, Hyun-Joon,Choi, Hwan Gun,Park, Chan Sun,Chang, Jae Won,Lee, Won Koo,Dong, Yongkwan,Yun, Hoseop
, p. 8267 - 8276 (2007/10/03)
Syntheses of cis-3-alkylaziridine-2-carboxylates including cis-3-benzyl- and cis-3-phenylaziridine-2-carboxylates were achieved from the reaction of α-aminonitrile and alkyldiazoacetate in the presence of a Lewis acid. Asymmetric version of this reaction with the chiral α-methylbenzylamine was also successful for the preparation of chiral aziridines that were used for the synthesis of various amino acids including homophenylalanine, β-amino-α-hydroxy acid, α,β-diamino acid, and α-amino-β-hydroxy acid via regioselective aziridine ring openings.
194. Diastereoselecktive Alkylation of 3-Aminobutanoic Acid in the 2-Position
Estermann, Heinrich,Seebach, Dieter
, p. 1824 - 1840 (2007/10/02)
The enantiomerically pure 3-aminobutanoic acids (R)- and (S)-6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-methyl 3-(benzoylamino)butanoate ((S)-3) is also available by enzymatic kinetic resolution with pig-liver esterase.The N-benzoyl- and N-benzyloxycarbonyl derivatives rac-3, 8,and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2).The configuration of three of the products is assigned (Schemes 4-6), and in four cases, the free α-substituted β-amino acid is prepared by acidic hydrolysis (see Table 3).It is shown that the doubly lithiated β-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.
