Total Synthesis of Gabosine H and Two Non-natural Gabosines

Dedicated to the memory of Prof. Dr. Dr. hc. Theophil Eicher without whom the development of the scientific research in our laboratory would not have been possible.

Abstract

Gabosines constitute a group of naturally occurring compounds with unique structures that exhibit very interesting biological activities. Synthetic efforts have been continuously reported since 1985. In this work, multistep total syntheses of natural gabosine H and non-natural gabosines have been accomplished by using a chemoenzymatic approach. Chirality was transferred from the starting material 3-methyl-cis-1,2-cyclohexadienediol, which was obtained by biotransformation of toluene. Protection of the diol followed by iodohydroxylation or dihydroxylation of the less hindered double bond and further functional group transformations, permitted us to build up the synthetic sequences to the final products. The chemical structures and the absolute configurations of two key intermediates and two final products were confirmed by X-ray diffraction.

Key words

gabosines - X-ray crystal structures - synthesis - enantioselectivity - chemoenzymatic reactions

• References

• 1 Tatsuta K, Tsuchiya T, Mikami N, Umezawa H, Naganawa H. J. Antibiot. 1974; 27: 579
• 2 Bayon P, Figueredo M. Chem. Rev. 2013; 113: 4680
• 3a Huntley CF. M, Hamilton DS, Creighton DJ, Ganem B. Org. Lett. 2000; 3143
• 3b Kamiya D, Uchihata Y, Ichikawa E, Kato K, Umezawa K. Bioorg. Med. Chem. Lett. 2005; 15: 1111
• 3c Bach G, Breiding MS, Grabley S, Hammann P, Hutter K, Thiericke R, Uhr H, Wink J, Zeeck A. Liebigs Ann. Chem. 1993; 3: 241
• 3d Das M, Manna K. Curr. Bioact. Compd. 2015; 11: 239
• 3e Tang Y.-Q, Maul C, Hofs R, Sattler I, Grabley S, Feng X.-Z, Zeeck A, Thiericke R. Eur. J. Org. Chem. 2000; 3353
• 4 Mac DH, Chandraksehar S, Greé R. Eur. J. Org. Chem. 2012; 5881
• 5 Mirza S, Molleyres L.-P, Vasella A. Helv. Chim. Acta 1985; 68: 988
• 6 Lygo B, Swiatyj M, Trabsa H, Voyle M. Tetrahedron Lett. 1994; 35: 4197
• 7 Tatsuta K, Yasuda S, Araki N, Takahashi M, Kamiya Y. Tetrahedron Lett. 1998; 39: 401
• 8 Shinada T, Fuji T, Ohtani Y, Yoshida Y, Ohfune Y. Synlett 2002; 1341
• 9 Ramana GV, Rao BV. Tetrahedron Lett. 2005; 46: 3049
• 10 Shing TK. M, Cheng HM. J. Org. Chem. 2007; 72: 6610
• 11 Shing TK. M, So KH, Kwok WS. Org. Lett. 2009; 11: 5070
• 12 Fresneda MA, Alibés R, Font J, Bayón P, Figueredo M. Org. Biomol. Chem. 2013; 11: 6562
• 13 Fresneda MA, Alibés R, Font J, Bayon P, Figueredo M. J. Org. Chem. 2012; 77: 5030
• 14 Fresneda MA, Alibés R, Bayón P, Figueredo M. Eur. J. Org. Chem. 2016; 3568
• 15 Raju G, Rao MV, Rao BV. J. Carbohydr. Chem. 2016; 35: 150
• 16 Babu DC, Rao CB, Venkatesham K, Selvam JJ. P, Venkateswarlu Y. Carbohydr. Res. 2014; 388: 130
• 17a Hudlicky T, Reed JW. Synlett 2009; 685
• 17b Boyd DR, Sharma ND, Malone JF, McIntyre PB. A, McRoberts C, Floyd S, Allen CC. R, Gohil A, Coles SJ, Horton PN, Stevenson PJ. J. Org. Chem. 2015; 80: 3429
• 18 Banwell MG, Bray AM, Wong DJ. New J. Chem. 2001; 25: 1351
• 19 Gibson DT, Koch J, Kallio R. Biochemistry 1968; 7: 2553
• 20 Labora M, Schapiro V, Pandolfi E. Tetrahedron: Asymmetry 2011; 22: 1705
• 21 Carrera I, Brovetto M, Seoane G. Tetrahedron 2007; 63: 4095
• 22 Macías MA, Suescun L, Pandolfi E, Schapiro V, Tibhe GD, Mombrú AW. Acta Crystallogr., Sect. E: Struct. Rep. Online 2015; 71: 1013
• 23 More JD, Finney NS. Org. Lett. 2002; 4: 3001
• 24 Prasad KR, Kumar SM. Synlett 2011; 1602
• 25 Vulovic B, Kolarski D, Bihelovic F, Matovic R, Gruden M. Org. Lett. 2016; 18: 3886
• 26 Brovetto M, Schapiro V, Cavalli G, Padilla P, Sierra A, Seoane G, Suescun L, Mariezcurrena R. New J. Chem. 1999; 23: 549