Yamada s synthesis

In nearly two decades, challenging structured of phomactins coupled with the interesting biological activity has elicited an impressive amount of synthetic efforts [16-18]. (+)-Phomactin D was first synthesized by Yamada in 1996 [19], and Wulff [20] reported the synthesis of ( )-phomactin B2 in 2007. However, (+)-phomactin A has been the most popular target because of its unique topology. To date, two monumental total syntheses have been accomplished Pattenden s [21] racemic synthesis and Halcomb s [22] asymmetric synthesis in 2002 and 2003, respectively. Both syntheses are beautifully done but also mimicked Yamada s synthesis of D, thereby underscoring the remarkable influence of Yamada s earlier work on the phomactin chemistry. Upon completing their synthesis of ( )-phomactin A, Pattenden [23] completed ( )-phomactin G via a modified route used for A. 

Except for Yamada s synthesis, all total syntheses feature the venerable Diels-Alder reaction as a key transformation, in either an intermolecular or intramolecular fashion or in a combination of both. 

The enantiomeric products can be obtained by use of the enamines derived from enantiomeric amino acids. Alternatively, the enantiomeric cyclohexanone can be obtained by chemical interconversion Sone, T. Terashima, S. Yamada, S. Synthesis 1974, 725-726. 

Reetz MT, Hiibel M, Jaeger R, Schwickardi R, Goddard R (1994) Synthesis 733 Seki M, Hatsuda M, Mori Y, Yoshida S, Yamada S, Shimizu T (2004) Chem Eur J 10 6102... 

T Miyazawa, T Otomatsu, Y Fukui, T Yamada, S Kuwata. Racemization-free and efficient peptide synthesis by the carbodiimide method using 1-hydroxybenzotriazole and copper(II) chloride simultaneously as additives. J Chem Soc Chem Commun 419, 1988. 

T Miyazawa, T Donkai, T Yamada, S Kuwata. Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the mixed-anhydride and related methods. Int J Pept Prot Res 40, 49, 1992. 

Ohya K, Yamada S, Felix R, Fleisch H. Effect of bisphosphonates on prostaglandin synthesis by rat bone-cells and mouse calvaria in culture. Clin Sci 1985 69 403 11. 

The versatility of polymer-assisted enzymatic synthesis of non-natural and biologically significant glycolipid derivatives was also demonstrated by constructing pseudo-ganglioside GM3, see K. Yamada, S. Matsumoto, S-I. Nishimura, Chem. Commun. 1999, 507-508. 

Fig. 11 Retrosynthetic overview of Yamada s ex-chiral-pool total synthesis of (-)-clae-none (42) (1998)...

In conclusion, the longest linear sequence of Yamada s (-)-claenone (42) synthesis consist of 40 steps (6 C/C connecting transformation) with an overall yield of 2.1%. The centrepiece of Yamada s synthetic strategy is the sequence of two Michael additions and a retro-aldol addition to provide a highly substituted cyclopentanone building block (52). 

The structural similarity between claenone (42) and stolonidiol (38) enabled Yamada to exploit an almost identical strategy for the total synthesis of (-)-stolonidiol (38) [40]. A short retrosynthetic analysis is depicted in Fig. 12. An intramolecular HWE reaction of 68 was successfully applied for the macrocyclization. The highly substituted cyclopentanone 69 was made available by a sequence that is highlighted by the sequential Michael-Mi-chael addition between the enolate 53 and the a, -unsaturated ester 70 followed by a retro-aldol addition. However, as is the case for the claenone (42) synthesis, the synthesis of stolonidiol (38) is characterized by numerous functional and protecting group transformations that are a consequence of Yamada s synthetic strategy. 

Shioiri T, Ninomiya K, Yamada S (1972) Diphenylphosphorylazide. A New Convenient Reagent for a Modified Curtius Reaction and for the Peptide Synthesis. J Am Chem Soc 94 6203... 

Yamada S, Ikota N, Shioiri T. Diphenyl phosphorazidate (DPPA) and diethyl phosphorocyanidate (DEPC). Two new reagents for solid-phase peptide synthesis and their application to the synthesis of porcine motilin. J. Am. Chem. Soc. 1975 97 7174-7175. 

Ikota N, Shioiri T, Yamada S, Tachibana S. Amino acids and peptides. XXXI. Phosphorus in organic synthesis. XVIII. Synthesis of porcine motilin by the solid-phase method us- 41. ing diphenyl phosphorazidate (DPPA) and diethyl phosphoro-cyanidate (DEPC). Chem. Pharm. Bull. 1980 28 3347-5336. 

Alternatively, after having governed the stereochemistry at C-1, the carboxy group at C-3 can be eliminated (Scheme 15), e.g. according to Yamada s method. Such as overall enantioselective synthesis of optically pure 1-alkyltetrahydro-p-carbolines from the chiral pool , optionally with (R) or (S) configuration, has been applied in numerous indol alkaloid syntheses. ... 

Shioiri, T., Ninomiya, K., Yamada, S. Diphenylphosphoryl azide. New convenient reagent for a modified Curtius reaction and for peptide synthesis. J. Am. Chem. Soc. 1972, 94, 6203-6205. 

Yamada, S., Hiroi, K., Achiwa, K. Asymmetric synthesis with amino acids. I. Asymmetric induction in the alkylation of ketone enamines. Tetrahedron Lett. 1969, 4233 236. 

Chida, N., Yamada, K., and Ogawa, S., Synthesis and absolute configuration of the naturally occurring cyano glucoside simmondsin. 7. Chem. Soc., Perkin Trans. 1, 1131, 1992. 

Takano, S., Yamada, S.L, Numata, H., and Ogasawara, K., A new synthesis of a steroid side chain via stereocontrolled protonation. Synthesis of (-)-desmosterol, J. Chem. Soc., Chem. Commun., 760, 1983. 

If there is already a chiral centre in the molecule that has already been controlled by asymmetric synthesis, the AE reaction will ignore it if it is far enough away. Yamada s synthesis10 of the biologically active diterpenoid 45 illustrates this and demonstrates control when nucleophiles attack an unsymmetrical epoxide. Preliminary disconnections with a Diels-Alder in mind took the chemists back to the diol 48. 

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