201210-25-5Relevant articles and documents
Total Synthesis and Structural Establishment/Revision of Antibiotics A54145
Chen, Delin,Chow, Hoi Yee,Po, Kathy Hiu Laam,Ma, Wenjie,Leung, Emily Lok Yee,Sun, Zhenquan,Liu, Ming,Chen, Sheng,Li, Xuechen
, p. 5639 - 5644 (2019)
A54145 is a family of antibacterial cyclic lipodepsipeptides structurally resembling daptomycin. Since its discovery in 1990, only the ambiguous structures of the methoxy-aspartic acid (MeO-Asp) and the hydroxy-asparagine (HO-Asn) have been reported. We have developed efficient routes to obtain the fully protected l-MeO-Asp and l-HO-Asn building blocks compatible with Fmoc-SPPS, and a total synthesis of A54145 that enabled us to establish its structure, consisting of l-3S-HO-Asn and l-3R-MeO-Asp, revising the wrongly proposed structure of l-3S-MeO-Asp.
The role of phosphopeptides in the mineralisation of silica
Daus, Fabian,Geyer, Armin,Hampp, Norbert,Pfeifer, Erik,Seipp, Kevin
supporting information, p. 700 - 706 (2020/02/11)
We investigated the silicification activity of hyperphosphorylated peptides in combination with long-chain polyamines (LCPA). The bioinspired in vitro silicification experiments with peptides containing different amounts of phosphorylated serines showed structure-activity dependence by altering the amount and morphology of the silica precipitate. Our study provides an explanation for the considerable metabolic role of diatoms in the synthesis of hyperphosphorylated poly-cationic peptides such as natSil-1A1. The efficient late-stage phosphorylation of peptides yielded a synthetic heptaphosphopeptide whose silicification properties resemble those of natSil-1A1. As opposed to this, unphosphorylated poly-cationic peptides or LCPA require concentrations above 1 mM for silicification. Hyperphosphorylated peptides showed a linear dependence between the amount of dissolved peptides and the amount of precipitated silica in the concentration range below 1 mM. Under mildly acidic conditions and short precipitation times, the concentration of the added LCPA determined the size of the silica spheres.
Convergent Synthesis of Calcium-Dependent Antibiotic CDA3a and Analogues with Improved Antibacterial Activity via Late-Stage Serine Ligation
Blasco, Pilar,Chen, Delin,Chen, Sheng,Li, Xuechen,Po, Kathy Hiu Laam
supporting information, (2020/06/29)
A convergent synthesis via the late-stage serine ligation of naturally occurring calcium-dependent antibiotic CDA3a and its analogues has been developed, which allowed us to readily synthesize the analogues with the variation on the lipid tail. Some analogues were found to show 100-500-fold higher antimicrobial activity than the natural compound CDA3a against drug resistant bacteria. This study will enhance our understanding of CDA3a and provide valuable antibacterial lead candidates for further development.
Total Synthesis of Scytonemide A Employing Weinreb AM Solid-Phase Resin
Wilson, Tyler A.,Tokarski, Robert J.,Sullivan, Peter,Demoret, Robert M.,Orjala, Jimmy,Rakotondraibe, L. Harinantenaina,Fuchs, James R.
, p. 534 - 542 (2018/03/30)
The human 20S proteasome inhibitor scytonemide A (1), a macrocyclic imine originally isolated from the cyanobacterium Scytonema hofmanni, was synthesized via a biomimetic solid-phase peptide synthesis (SPPS) approach employing the Weinreb AM resin. Utilizing this approach, cyclization of the protected heptapeptide via formation of the imine bond occurred spontaneously upon cleavage from the resin in the presence of a reducing agent and subsequent aqueous workup. The final deprotection step necessary to produce the natural product was accomplished under slightly basic conditions, facilitating cleavage of the silyl ether group while leaving the macrocycle intact. Purification of the synthetic scytonemide A was accomplished via normal-phase flash column chromatography, potentially facilitating larger scale preparation of the compound necessary for future mechanistic and SAR studies. The structure of the target compound was confirmed by NMR spectroscopy, which also shed light on differences in the spectroscopic data obtained for the synthetic and natural scytonemide A samples for some of the amide and alcohol signals in the 1H NMR spectrum.
Sterically biased 3,3-sigmatropic rearrangement of azides: Efficient preparation of nonracemic α-amino acids and heterocycles
Gagnon, David,Lauzon, Sophie,Godbout, Cedrickx,Spino, Claude
, p. 4769 - 4771 (2007/10/03)
(Chemical Equation Presented) Homochiral α-amino acids, heterocycles, and carbocycles are efficiently constructed via a short sequence of reactions starting from the chiral auxiliary p-menthane-3-carboxaldehyde. The key feature of the sequence is a highly selective tandem Mitsunobu/3,3-sigmatropic rearrangement of hydrazoic acid that procures enantiomerically enriched allylic azides. The sequence is either terminated by oxidative cleavage to provide amino acids or by ring-closing metathesis to provide heterocycles or carbocycles bearing nitrogen.
Synthesis of N-protected N-methyl serine and threonine
Luo, Yue,Evindar, Ghotas,Fishlock, Dan,Lajoie, Gilles A
, p. 3807 - 3809 (2007/10/03)
Two efficient and convenient syntheses of N-Cbz and N-Fmoc N-methyl serine and threonine are described. The amino acid side-chain alcohol can be protected as a TBDMS ether in very good yield or left free, followed by the formation and subsequent reduction of the corresponding oxazolidinone.
Application of t-Butyldimethylsilyl Ethers of Serine, Threonine and Tyrosine in Peptide Synthesis
Fischer, Peter M.
, p. 7605 - 7608 (2007/10/02)
The utility of Tbdms (t-butyldimethylsilyl) ethers, prepared conveniently in a one pot procedure from Nα-Fmoc (9-fluorenylmethoxycarbonyl) and Nα-Z (benzyloxycarbonyl) hydroxyamino acids, is demonstrated: peptide bond formation and esterification to 4-alkoxybenzylalcohol resin are achieved readily with these derivatives.The lability of the Tbdms ethers to various reagents enables selective deprotection of the hydroxyl side-chains assembly, desirable, e.g., for phosphorylation of glycosylation.
