134 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 134–135 J. Chem. Research (M), 1997, 0901–0924 Synthesis of New Naturally Occurring 6-Deoxo Brassinosteroids Suguru Takatsuto,*a Tsuyoshi Watanabe,b Shozo Fujiokac and Akira Sakuraic aDepartment of Chemistry, Joetsu University of Education, Joetsu-shi, Niigata 943, Japan bTama Biochemical Co. Ltd., 2-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 163, Japan cThe Institute of Physical and Chemical Research (RIKEN), Wako-shi, Saitama 351-01, Japan New natural 6-deoxo brassinosteroids, 6-deoxoteasterone 1, 3-dehydro-6-deoxoteasterone 2 and 6-deoxotyphasterol 3, as well as 6-deoxocastasterone 4, are synthesized from (20S)-20-formyl-6b-methoxy-3a,5-cyclo-5a-pregnane 5.The occurrence of new 6-deoxo brassinosteroids (BRs), 6-deoxoteasterone 1, 3-dehydro-6-deoxoteasterone 2 and 6-deoxotyphasterol 3, along with 6-deoxocastasterone 4 (Fig. 1) in plants, has been demonstrated.3,4,6 Recently, we have identified 6-deoxotyphasterol 3, 6-deoxocastasterone 4, typhasterol and castasterone in a wild type of Arabidopsis thaliana, suggesting the possibility that both the late and early C6-oxidation pathways4 of the BR biosynthesis are operating in A.thaliana.9 In order to establish the involvement of the late C6-oxidation pathway of the brassinolide biosynthesis in A. thaliana, the 6-deoxo BRs (1, 2, 3 and 4) are required as authentic specimens. It is also necessary to evaluate their biological activities.Because of the scarcity of the natural products, we now describe the synthesis of these 6-deoxo BRs. The side chain of these 6-deoxo BRs was constructed in six steps (Scheme 1) in 26% overall yield from the known C-22-aldehyde 5.12 The key reactions for the construction of the (22R,23R,24S)-side chain of these C28 BRs are the reaction of the C-22-aldehyde 5 with the Grignard reagent derived from (Z)-1-bromoprop-1-ene, orthoester Claisen rearrangement13 of the resulting (22S,23Z)-allylic alcohol, and the asymmetric dihydroxylation10 of the crinosterol side chain.As the transformation of the diol 9 into brassinolide is *To receive any correspondence. Fig. 1 Structure of 6-deoxo brassinosteroids 1–4 Scheme 1 Reagent and conditions: i, BrMgCH�CHCH3, THF, 0 °C to room temp., 1 h; ii, Et(OEt)3, propionic acid, xylene, reflux, 2 h; iii, LiAlH4, THF, reflux, 2 h; iv, MeSO2Cl, Et3N, toluene, room temp., 2 h; v, OsO4, K3[Fe(CN)6], dihydroquinidine p-chlorobenzoate, K2CO3, methanesulfonamide, ButOH–H2O, room temp., 15 d Scheme 2 Reagent and conditions: i, TsOH, aq.dioxane, reflux, 4 h; ii, H2/Pd–C, EtOH, 40 °C, 2 h; iii, TsOH, acetone, room temp., 1 h; iv, MeSO2Cl, pyridine, room temp., 1 h; v, KO2, 18-crown-6, DMSO–DMF, room temp., 2 h; vi, 70% aq. AcOH, 100 °C, 4 h; vii, 5% KOH–MeOH, room temp., 1 h; viii, PCC, CH2Cl2, room temp., 1 h; ix, Li2CO3, DMF, 170 °C, 1 h; x, OsO4, NMO, aq. THF, room temp., 4 hJ. CHEM.RESEARCH (S), 1997 135 known,18 the formal synthesis of brassinolide was achieved. We next modified the A/B ring of the diol 9 for the target 6-deoxo BRs (Scheme 2). Regeneration of a 5-en-3b-ol system followed by hydrogenation provided 6-deoxoteasterone 1 quantitatively, which was converted to the sulfonate 11. Introduction of the 3a-hydroxy and 2-ene functionality was achieved in 66 and 71% yield, respectively. The 3a-alcohol 12 was deprotected to afford 6-deoxotyphasterol 3.The alcohol 12 was oxidized to give, after deprotection, 3-dehydro- 6-deoxoteasterone 2 in 83% yield. Introduction of the 2a,3a-diol group into the 2-ene 14 followed by deprotection afforded 6-deoxocastasterone 4 in 72% yield. In conclusion, we have developed a convenient method to construct the (22R,23R,24S) side chain of natural C28 BRs and synthesized three new 6-deoxo BRs (1, 2 and 3) and also 6-deoxocastasterone 4. The method is also suitable for the preparation of biosynthetically important 6-oxo BRs such as teasterone, 3-dehydroteasterone, typhasterol and castasterone.Techniques used: 1H and 13C NMR, EI-MS, EI-HR-MS, FAB-MS References: 38 Figure: 1 Schemes: 2 Received, 10th December 1996; Accepted, 17th January 1997 Paper E/6/08323D References cited in this synopsis 3 P. G. Griffiths, J. M. Sasse, T. Yokota and D. W. Cameron, Biosci. Biotech. Biochem., 1995, 59, 956. 4 Y.-H. Choi, S. Fujioka, T. Nomura, A. Harada, T. Yokota, S. Takatsuto and A. Sakurai, Phytochemistry, 1997, 44, 609. 6 Y.-H. Choi, S. Fujioka, A. Harada, T. Yokota, S. Takatsuto and A. Sakurai, Phytochemistry, 1996, 43, 593. 9 S. Fujioka, Y.-H. Choi, S. Takatsuto, T. Yokota, J. Li, J. Chory and A. Sakurai, Plant Cell Physiol., 1996, 37, 1201. 10 (c) W. Amberg, Y. L. Bennani, R. K. Chadha, G. A. Crispino, W. D. Davis, J. Hartung, K.-S. Jeong, Y. Ogino, T. Shibata and K. B. Sharpless, J. Org. Chem., 1993, 58, 844. 12 (a) D. G. 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