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Total synthesis
About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.
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93 citations
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TL;DR: The available evidence indicates that the ease of formation of the disulfide bond A7–B7 does not depend on the precursor molecule already having an insulin-like conformation.
Abstract: Total synthesis of human insulin. IV. Description of the final steps.
Recently a preliminary account was given of a new synthetic pathway leading to human insulin. In the present report the last steps of this synthesis – i.e. as from the unsymmetrical cystine derivative I – are described in detail. I contains the sequences A(14–21) and B(17–30), linked by the disulfide bridge A20-B19. These last steps are: (1) selective removal by pH-controlled acidolysis in trifluoroethanol of N(α)-Trt from leucine B17, (2) completion of the B-chain by coupling with the fragment B(1–16), (3) selective removal by trifluoroethanol of N(α)-Bpoc at tyrosine A14, (4) completion of the A-chain by coupling with the cyclic fragment A(1–13), (5) removal of the acid labile protecting groups, and (6) formation of the disulfide bond A7–B7 from the two S-acetamido-protected cysteine residues by treatment with iodine.
As judged by the composition of the reaction mixture the closure of the 85-membered ring proceeds with a cyclization yield of over 70%. From the last step in the synthesis two products were obtained after extensive purification by counter-current distribution: pure human insulin in a yield of 50% and its [D-tyrosine B16]Isomer in a yield of 25%. Although the partial racemization of tyrosine B16 occurred during coupling with sequence B(1–16), the [D-tyrosine B 16]-stereoisomer could only be separated at the endproduct stage.
The available evidence indicates that the ease of formation of the disulfide bond A7–B7 does not depend on the precursor molecule already having an insulin-like conformation.
93 citations
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TL;DR: The total synthesis of the polyether antibiotic ionomycin, a calcium ionophore, is described, demonstrating the utility of ring-opening methodologies as applied to the synthesis of polypropionate and deoxypolyPropionate subunits.
93 citations
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93 citations
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TL;DR: The first total synthesis of (±)-huperzine A, a new lycopodium alkaloid, was described in this paper, where the synthesis was carried out in the early 1990s.
93 citations