Proline revised

In 1963 a group of Swiss authors (12) isolated zizyphine from Zizyphus oenoplia and recognized isoleucine and proline as components. Two years later Zbiral etal. (13) proposed a complete structure which was later revised (14). Pais et al. (15) in an earlier preliminary report suggested the structure of pandamine which had been isolated from Panda oleosa. This was confirmed in 1966, and the structure of the similarly constituted pandamine was reported (17). Shortly thereafter Tschesche and co-workers (18) reported the structure of an alkaloid of this type scutianine-A from Scutia buxifolia. Since then the number of cyclopeptide alkaloids of known structure has risen to more than sixty, a figure which Klein and Rapoport had envisioned in 1968 (20). The workers at Gif-sur-Yvette and at Bonn have been in the forefront of these researches but others have made important contributions (19-26). 

Our best theoretical values suggest that the experimental gas-phase heats of formation from the NIST WebBook should be revised downward by 2.4 (alanine), 0.7-0.8 (glycine), 3.2 (methionine), and 5.3 (proline) kcal/mol. Similarly, we suggest that the experimental values from the... 

In 2008, MacMillan and co-workers [13] reported the first total synthesis and structure revision of callipeltoside C (38), a cytotoxic marine macrolide, with amino acid proline as a suitable organocatalyst for the construction of three key intermediates. This elegant synthesis (18 steps, 12% overall yield) demonstrated the power of organocatalysis with unprecedented level of ease and efficiency, which involved a proline-catalyzed double diastereo-differentiating aldol reaction between propionaldehyde 18 and the Roche ester-derived aldehyde 28 to achieve 29 (12 1 dr, 99% ee), an organocatalytic a-oxyamination to afford 32 (99% ee), and proline-... 

The overall synthetic strategy toward the tetrapeptide scaffold of telaprevir requires four key amino acid building blocks (45-49, Scheme 8), which can be coupled using standard peptide coupling methods. As in the synthesis of boceprevir, the P2 domain (48), which contains the bicyclic proline mimic, is the most synthetically challenging fragment of telaprevir, particularly in the context of a scalable route for commercialization. Likewise, the synthesis of the PI ketoamide domain (49) has required significant revision and optimization in the transition from discovery to process scale. 

In 1963, Felix and Hashimoto revised their earlier results on the N-terminals and the amino-acid composition of unfractionated clupeine from Clupea harengus so that there was no longer any essential difference in material from the two herring species. A sample of unfractionated clupeine from North Sea herring sperm heads was prepared again in the late Prof. Felix s laboratory in Frankfurt am Main in March 1963 and sent to Prof. Ando s laboratory in Tokyo for use in structural studies. This sample was found to be not different from unfractionated clupeine from Pacific herring as regards amino-acid composition, N-terminal amino acids (proline, 36% and alanine, 64%), N-terminal sequences (Pro-Arg and Ala Arg-Arg ), and tryptic peptides (Thr.Thr 0.95, Thr Arg 0.84, Val Ser Arg 1.7, Pro Val Arg 0.33, Pro He Arg 0.12, Ala Gly Arg 1.03, Ser Arg 0.52, Ala Ser Arg 0.27, Ala Arg 3.54, Ser-Ser-Ser-Arg-Pro-He-Arg 0.7g, Pro-Arg O.87, Ala Ser Arg Pro-Val-Arg I.O2, Arg 8.16, Arg-Pro-Arg 1.5, Ala-Arg-Arg 0.5, Arg-Arg 10.2 moles/3 moles clupeine) (Nukushina, 1964 Nukushina 1964). 

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