Simple and Efficient Routes to Optically Active chiro- and allo-Inositol Derivatives from myo-Inositol

Abstract

Efficient routes for the gram scale syntheses of optically active chiro- and allo-inositol derivatives from readily available 1,2:4,5-di-O-isopropylidene-myo-inositol (1) are described. Both d and l forms of these isomeric inositols could be synthesized from enantiomers of 1. One-pot methodology for the simultaneous synthesis of both chiro and allo has also been developed. The possible selectivity for the cleavage of trans-ketal in presence of the cis is an added advantage for the syntheses of a variety of protected deri­vatives for phosphoinositol syntheses. These routes provide synthetically flexible 1,2:4,5-di-O-isopropylidene-chiro-inositol and 1,6:3,4-di-O-isopropylidene-allo-inositol which are difficult to achieve otherwise.

Key words

cyclitols - inositols - regioselectivity - carbohydrates - ­inhibitors

References

• 1 Berridge MJ. Nature (London, U.K.)  1993,  361:  315 
• 2a Hinchliffe K. Irvine R. Nature (London, U.K.)  1997,  390:  123 
• 2b Phosphoinositides: Chemistry, Biochemistry and Biomedical Applications   ACS Symposium Series 718:  Bruzik KS. ACS; Washington DC: 1999. 
• 3 Ferguson MAJ. Williams AF. Annu. Rev. Biochem.  1988,  57:  285 
• 4a Kwon Y.-K. Lee C. Chung S.-K. J. Org. Chem.  2002,  67:  3327 
• 4b Suzuki T. Suzuki ST. Yamada I. Koashi Y. Yamada K. Chida N. J. Org. Chem.  2002,  67:  2874 
• 4c Chida N. Ogawa S. Chem. Commun.  1997,  807 ; and references cited therein
• 4d Suzuki T. Tanaka S. Yamada I. Koashi Y. Yamada K. Chida N. Org. Lett.  2000,  2:  1137 
• 4e Chida N. Yoshinaga M. Tobe T. Ogawa S. Chem. Commun.  1997,  1043 
• 5 Sureshan KM. Shashidhar MS. Varma AJ. J. Org. Chem.  2002,  67:  6884 ; and references cited therein
• 6 Hosoda A. Miyake Y. Nomura E. Taniguchi H. Chem. Lett.  2003,  32:  1042 
• 7 Akiyama T. Hara M. Fuchibe K. Sakamoto S. Yamaguchi K. Chem. Commun.  2003,  1734 
• 8 Sureshan KM. Gonnade RG. Shashidhar MS. Puranik VG. Bhadbhade MM. Chem. Commun.  2001,  881 
• 9a Chiara JL. Valle N. Tetrahedron: Asymmetry  1995,  6:  1895 
• 9b Brammer LE. Hudlicky T. Tetrahedron: Asymmetry  1998,  9:  2011 
• 9c Kornienko A. d’Alarco M. Tetrahedron Lett.  1997,  38:  6497 
• 9d Chung S.-K. Yu S.-H. Bioorg. Med. Chem. Lett.  1996,  6:  1461 
• 9e Berlin WK. Zhang W.-S. Shen TY. Tetrahedron  1991,  47:  1 
• 9f Jaramillo C. Chiara J.-L. Martin-Lomas M. J. Org. Chem.  1994,  59:  3135 
• 9g Mandel M. Hudlicky T. J. Org. Chem.  1993,  58:  2331 
• 9h Kornienko A. Marnera G. d’Alarco M. Carbohydr. Res.  1998,  310:  141 
• 9i Catelani G. Corsaro A. d’Andrea F. Mariani M. Pistara V. Bioorg. Med. Chem. Lett.  2002,  12:  3313 
• 9j Jaramillo C. Martin-Lomas M. Tetrahedron Lett.  1991,  32:  2501 
• 9k Kim KS. Park J. Moon HK. Yi H. Chem. Commun.  1998,  1945 
• 9l Carless HAJ. Busia K. Oak OZ. Synlett  1993,  672 
• 9m Pistara V. Barili PL. Catelani G. Corsaro A. D’Andrea F. Fisichella S. Tetrahedron Lett.  2000,  41:  3253 
• 9n Mehta G. Lakshminath S. Tetrahedron Lett.  2000,  41:  3509 
• 9o Desjardins M. Brammer LE. Hudlicky T. Carbohydr. Res.  1997,  304:  39 
• 9p Mandel M. Hudlicky T. J. Chem. Soc., Perkin Trans. 1  1993,  741 
• 9q Hudlicky T. Restrepo-Sanchez N. Kary PD. Jaramillo-Gomez LM. Carbohydr. Res.  2000,  324:  200 
• 9r Angyal SJ. Odier L. Tate ME. Carbohydr. Res.  1995,  266:  143 
• 10 Sureshan KM. Shashidhar MS. Praveen T. Das T. Chem. Rev.  2003,  103:  4477 
• Although optically active inositol derivatives can be made from sugar derivatives via Ferrier type cyclization, the yield of such C-C coupling is known to vary greatly. Also synthetic steps become too lengthy. But recently an elegant synthesis of all inositol derivatives in optically pure form via Ferrier cyclization followed by stereoselective reduction was reported, see:
• 11a Takahashi H. Kittaka H. Ikegami S. J. Org. Chem.  2001,  66:  2705 
• 11b Takahashi H. Kittaka H. Ikegami S. Tetrahedron Lett.  1998,  39:  9707 
• 12a Husson C. Odier L. Vottero PJA. Carbohydr. Res.  1998,  307:  163 
• 12b Lampe D. Liu C. Mahon MF. Potter BVL. J. Chem. Soc., Perkin Trans. 1  1996,  1717 
• 12c Lee HW. Kishi Y. J. Org. Chem.  1985,  50:  4402 
• 12d Chung S.-K. Kwon Y.-U. Chang Y.-T. Sohn K.-H. Shin J.-H. Park K.-H. Hong B.-J. Chung I.-H. Bioorg. Med. Chem.  1999,  7:  2577 
• 12e Sarmah MP. Shashidhar MS. Carbohydr. Res.  2003,  338:  999 
• 12f Roemer S. Stadler C. Rudolf MT. Jastorff B. Schultz C. J. Chem. Soc., Perkin Trans. 1  1996,  1683 
• 13 Riley AM. Jenkins DJ. Potter BVL. Carbohydr. Res.  1998,  314:  277 
• 14 Angyal SJ. Hickman RJ. Carbohydr. Res.  1971,  20:  97 
• 15 Takahashi Y. Nakayama H. Katagiri K. Ichikawa K. Ito N. Takita T. Takeuchi T. Miyake T. Tetrahedron Lett.  2001,  42:  1053 
• 16 Cid MB. Alfonso F. Martin-Lomas M. Synlett  2003,  1370 
• 17 Chung S.-K. Kwon Y.-U. Bioorg. Med. Chem. Lett.  1999,  9:  2135 
• 18 Kwon Y.-U. Im J. Choi G. Kim Y.-S. Choi KY. Chung S.-K. Bioorg. Med. Chem. Lett.  2003,  13:  2981 
• 19 Sureshan KM. Yamasaki T. Hayashi M. Watanabe Y. Tetrahedron: Asymmetry  2003,  14:  1771 
• 21 Suri SC. Rogers SL. Radhakrishnan KV. Nair V. Synth. Commun.  1996,  26:  1031 

20

This compound did not melt on heating but charred in the temperature range 110-130 °C.

22

To a solution of diol 1D (260 mg, 1 mmol) and pyridine (2 mL) in CH₂Cl₂ (10 mL) was added Tf₂O (255µL, 1.5 mmol) dropwise at -20 °C. The reaction mixture was stirred overnight at r.t. The solvents were evaporated and the residue was dissolved in EtOAc, washed successively with H₂O, cold diluted HCl, sat. aq NaHCO₃ and brine, dried (Na₂SO₄) and evaporated. The crude mixture of 3D and 4D thus obtained was dissolved in DMA (7 mL) and reacted with KOAc (500 mg, 5 mmol) at 70-80 °C for 5 h. DMA was evaporated and usual work-up of the residue followed by column chromatography yielded 5L (124 mg, 41%) and 8D (186 mg, 54%).