Gates, Marshall

Stockman BJ, Waldon DJ, Gates JA, Schaill TA, Kloosterman DA, Mizsak SA, Jacobsen EJ, Belonga KL, Mitchell MA, Mao B, Petke JD, Goodman L, Powers EA, Ledbetter SR, Kaytes PS, Yogeli G, Marshall VP, Petzold GL, Poorman RA. Solution structure of stromelysin complexed to thiadiazole inhibitors. Prot Sci 1998 7 2281-2286. 

The structure of morphine was first determined in 1925 by Sir Robert Robinson (1886— 1975) and John Masson Gulland (1898-1947). A total synthesis of morphine was achieved in 1952 at the University of Rochester by Marshall D. Gates (1915—2003) and his co-worker Gilg Tschudi. Since its first synthesis, a number of other processes have been used to synthesize morphine in the laboratory, but none of these is economically viable. Therefore morphine continues to be obtained through biosynthesis from poppy plants. 

However, despite the convincing results obtained at Miinchen and Harvard, there was also a certain amount of scepticism, for example, by Jack Dunitz as well as by Marshall Gates, the assistant editor of the Journal of the American Chemical Society. In a letter to Woodward he wrote We have dispatched your communication to the printers but I cannot help feeling that you have been at the hashish again. Remarkable seems a pallid word with which to describe this substance [13]. The sceptical voices disappeared when Philip Frank Eiland and Ray Pepinsky reported a complete X-ray crystal structure analysis of Fe(C5H5)2... 

If the peptide aggregate is envisioned as a molten globule, one plausible mechanism (Marshall, unpublished Figure 19) for gating of a pore formed by a helical bundle embedded in the membrane is a simple reorientation of helices. a-Helices have orientations of side chains that favor nonparallel association with an angle of approximately 25° between helix axes to pack optimally (see discussion and references cited in Chou et al. (296)) as seen in the transmembrane helices of the photosynthetic reaction center (252) and of bacteriorhodopsin (297). The surface tension of the membrane tends to minimize the volume of the helical bundle. The gating potential could simply be sufficient to force the helical elements to align with the potential field with a concommitant separation of helices due to the increased steric interaction... 

In 1952, Marshall D. Gates and Gilg Tschudi reported the first total synthesis of morphine. [93, 94] Since then, about 20 syntheses of racemic morphine have been published. [95] Only in 1993, Larry E. Overman could obtain (-)-mor-phine by an enantioselective synthesis. [96] Further syntheses followed in 1996 by Johann Mulzer [97], in 1997 by James White [98], in 2002 by Douglas Taber [99] andBarryTrost [100], and bymany others [101] as well (Tab. 5.6). Measured by the number of stages and the overall yield, the total syntheses by Rice in 1980 and Trost in 2002 are particularly noteworthy. 

Hartshome RS, Reardon CL, Ross D, Nuester J, Clarke TA, Gates AJ, Mills PC, Fredrickson JK, Zachara JM, Shi L, Beliaev AS, Marshall MJ, Tien M, Brantley S, Butt JN, Richardson DJ. Characterization of an electron conduit between bacteria and the extracellular environment. Proc Natl Acad Sci USA 2009 106 22169-22174. 

The opium poppy Papaver somniferum) makes morphine starting from the amino acid tyrosine. Morphine s structure was not finally solved until 1925 by Sir Robert Robinson. The first total synthesis in a chemistry lab was first achieved by Marshall and Gates in 1952. Making it in the lab is much more complicated and expensive than the natural route, so commercially morphine is obtained from poppies. 

The first synthesis of morphine was reported by Marshall Gates (University of Rochester). It was a remarkable achievement. The plan is outlined briefly here. The idea was that if compound 6 could be obtained, it would be possible to move forward to morphine. In parallel studies it was shown that morphine could be degraded to 6, thus providing a relay point for any synthesis effort, since morphine was in abundant supply and synthetic 6 would no doubt be difficult to obtain in large quantities. Structure 6 could clearly be obtained through a cycloaddition of an appropriate dienophile with 1,3-butadiene. The question is which dienophile. The choice ulitimately became o-naphthoquinone 8. A cycloaddition between this electron-deficient dienophile and 1,3-butadiene would provide 7, which one might convert to 6 via a reductive amination and additional oxidation state adjustments. 

---