Intramolecular Aglycon Delivery (IAD): The Solution to 1,2-cis Stereocontrol for Oligosaccharide Synthesis?

Abstract

Intramolecular glycosylation of a glycosyl acceptor temporarily tethered to the 2-hydroxyl group of the glycosyl donor, commonly referred to as Intramolecular Aglycon Delivery (IAD), potentially provides a solution to the perennial problem of how to synthesise 1,2-cis glycosidic linkages with complete stereocontrol. This account summarises developments in this area, focussing on the development within our group of intramolecular glycosylation based on allyl protecting groups (allyl IAD). Optimisation, the current scope and limitations, and further potential developments of allyl IAD are discussed herein.

• 1 Introduction

• 2 Intramolecular Aglycon Delivery (IAD): Previous Approach­es

• 2.1 Synthesis of β-Mannosides

• 2.2 Synthesis of Other 1,2-cis Glycosides by IAD

• 3 NIS-mediated Hindsgaul IAD

• 4 Allyl IAD

• 4.1 Thioglycoside Donors

• 4.2 Glycosyl Fluoride Donors

• 4.3 Attempted Facile Synthesis of (1-4) Linked Disaccharides

• 4.4 Extension to Other Sugars and Protecting Group Patterns

• 4.5 Optimisation

• 4.6 Mechanistic Studies

• 4.7 Iterative Oligosaccharide Synthesis

• 5 Summary and Future Perspectives

carbohydrates - glycosylations - stereoselective - intramolecular aglycon delivery (IAD) - 1,2-cis-glycosides

References

<A NAME="RA32203ST-1A">1a</A> Varki A. Glycobiology  1993,  3:  97 

<A NAME="RA32203ST-1B">1b</A> Dwek RA. Chem. Rev.  1996,  96:  683 

<A NAME="RA32203ST-2">2</A> For a series of articles outlining the potential of carbohydrates as therapeutic agents and also outlining recent advances in the fields of carbohydrate chemistry and glycobiology see: Science  2001,  291:  2338 

For some recent reviews of oligosaccharide synthesis see:

<A NAME="RA32203ST-3A">3a</A> Boons G.-J. Tetrahedron  1996,  52:  1095 

<A NAME="RA32203ST-3B">3b</A> Davis BG. J. Chem. Soc., Perkin Trans. 1  2000,  2137 

<A NAME="RA32203ST-4">4</A> See: Roth J. Chem. Rev.  2002,  102:  285 ; and references contained therein

<A NAME="RA32203ST-5">5</A>

Our main interest in accessing tetrasaccharide 1 was in order to determine its solution conformation by a series of NMR experiments in a variety of different solvents. However, as an offshoot of any synthesis we undertook we also desired access to a variety of truncated and fluorescence labeled sub-structures for use in enzyme assays amongst other purposes.

<A NAME="RA32203ST-6">6</A> Wulff G. Röhle G. Angew. Chem., Int. Ed. Engl.  1974,  13:  157 

<A NAME="RA32203ST-7">7</A> For a recent review on 1,2-cis glycosylation focussing on intermolecular approaches see: Demchenko AV. Curr. Org. Chem.  2003,  7:  35 

<A NAME="RA32203ST-8">8</A> Ogawa T. Nukada T. Kitajima T. Carbohydr. Res.  1983,  123:  C12 

<A NAME="RA32203ST-9A">9a</A> Lemieux RU. James K. Nagabhushan TL. Can. J. Chem.  1973,  51:  42 

<A NAME="RA32203ST-9B">9b</A> Lemieux RU. Hendriks KB. Stick RV. James K. J. Am. Chem. Soc.  1975,  97:  4056 

<A NAME="RA32203ST-10">10</A> For a recent review on intramolecular glycosylation see: Jung K.-H. Müller M. Schmidt RR. Chem. Rev.  2000,  100:  4423 

<A NAME="RA32203ST-11A">11a</A> Barresi F. Hindsgaul O. J. Am. Chem. Soc.  1991,  113:  9377 

<A NAME="RA32203ST-11B">11b</A> Barresi F. Hindsgaul O. Synlett  1992,  759 

<A NAME="RA32203ST-11C">11c</A> Barresi F. Hindsgaul O. Can. J. Chem.  1994,  72:  1447 

<A NAME="RA32203ST-12A">12a</A> Stork G. Kim G. J. Am. Chem. Soc.  1992,  114:  1087 

<A NAME="RA32203ST-12B">12b</A> Stork G. La Clair JJ. J. Am. Chem. Soc.  1996,  118:  247 

<A NAME="RA32203ST-13">13</A> Tebbe FN. Parshall GW. Reddy GS. J. Am. Chem. Soc.  1978,  100:  3611 

<A NAME="RA32203ST-14">14</A> Ito Y. Ogawa T. Angew. Chem. Int. Ed. Engl.  1994,  33:  1765 

<A NAME="RA32203ST-15">15</A> Ito Y. Ohnishi Y. Ogawa T. Nakahara Y. Synlett  1998,  1102 

<A NAME="RA32203ST-16A">16a</A> Dan A. Ito Y. Ogawa T. J. Org. Chem.  1995,  60:  4680 

<A NAME="RA32203ST-16B">16b</A> Dan A. Ito Y. Ogawa T. Tetrahedron Lett.  1995,  36:  7487 

<A NAME="RA32203ST-17A">17a</A> Lergenmüller M. Nukada T. Kuramochi K. Dan A. Ogawa T. Ito Y. Eur. J. Org. Chem.  1999,  1367 

<A NAME="RA32203ST-17B">17b</A> Ito Y. Ando H. Wada M. Kawai T. Ohnishi Y. Nakahara Y. Tetrahedron  2001,  57:  4123 

<A NAME="RA32203ST-18">18</A> Ito Y. Ogawa T. J. Am. Chem. Soc.  1997,  119:  5562 

<A NAME="RA32203ST-19A">19a</A> Bols M. J. Chem. Soc., Chem. Commun.  1992,  913 

<A NAME="RA32203ST-19B">19b</A> Bols M. J. Chem. Soc., Chem. Commun.  1993,  791 

<A NAME="RA32203ST-19C">19c</A> Bols M. Hansen HC. Chem. Lett.  1994,  1049 

<A NAME="RA32203ST-20">20</A> Packard GK. Rychnovsky SD. Org. Lett.  2001,  3:  3393 

<A NAME="RA32203ST-21A">21a</A> Krog-Jensen C. Oscarson S. J. Org. Chem.  1996,  61:  4512 

<A NAME="RA32203ST-21B">21b</A> Krog-Jensen C. Oscarson S. J. Org. Chem.  1998,  63:  1780 

<A NAME="RA32203ST-22">22</A> Gelin M. Ferrieres V. Lefeuvre M. Plusquellec D. Eur. J. Org. Chem.  2003,  1285 

<A NAME="RA32203ST-23">23</A> Ennis SC. Fairbanks AJ. Tennant-Eyles RJ. Yeates HS. Synlett  1999,  1387 

<A NAME="RA32203ST-24">24</A> The anomeric configurations of all mannosides synthesised throughout these studies were confirmed by measurement of the J _H-1,C-1 coupling constants which were in all cases less than 160 Hz, see: Bock K. Pedersen C. J. Chem. Soc., Perkin Trans. 2  1974,  293 

<A NAME="RA32203ST-25">25</A> Ennis SC. Fairbanks AJ. Slinn CA. Tennant-Eyles RJ. Yeates HS. Tetrahedron  2001,  57:  4221 

<A NAME="RA32203ST-26">26</A> Boons G.-J. Isles S. J. Org. Chem.  1996,  61:  4262 

<A NAME="RA32203ST-27">27</A> Seward CMP. Cumpstey I. Aloui M. Ennis SC. Redgrave AJ. Fairbanks AJ. Chem. Commun.  2000,  1409 

<A NAME="RA32203ST-28">28</A> Cumpstey I. Fairbanks AJ. Redgrave AJ. Org. Lett.  2001,  3:  2371 

<A NAME="RA32203ST-29">29</A> Mukaiyama T. Murai Y. Shoda S. Chem. Lett.  1981,  431 

<A NAME="RA32203ST-30">30</A> Cumpstey I. Fairbanks AJ. Redgrave AJ. Monatsh. Chem.  2002,  133:  449 

<A NAME="RA32203ST-31">31</A> Cumpstey I. D. Phil. Thesis   University of Oxford; UK: 2002. 

<A NAME="RA32203ST-32A">32a</A> Montchamp J.-L. Tian F. Hart ME. Frost JW. J. Org. Chem.  1996,  61:  3897 

<A NAME="RA32203ST-32B">32b</A> Douglas NL. Ley SV. Osborn HMI. Owen DR. Priepke HWM. Warriner SL. Synlett  1996,  793 

<A NAME="RA32203ST-33">33</A> Aloui M. Chambers D. Cumpstey I. Fairbanks AJ. Redgrave AJ. Seward CMP. Chem.-Eur. J.  2002,  8:  2608 

<A NAME="RA32203ST-34">34</A> Seward CMP. D. Phil. Thesis   University of Oxford; UK: 2002. 

<A NAME="RA32203ST-35">35</A> See for example: Scheffler G. Behrendt ME. Schmidt RR. Eur. J. Org. Chem.  2000,  3527 

<A NAME="RA32203ST-36">36</A> Ennis SC. Cumpstey I. Fairbanks AJ. Butters TD. Mackeen M. Wormald MR. Tetrahedron  2002,  58:  9403 

<A NAME="RA32203ST-37">37</A>

Cumpstey, I.; Fairbanks, A. J. unpublished results.

<A NAME="RA32203ST-38">38</A>

In fact both of these glycosylation reactions have only been performed on a single occasion on a small scale and so the reaction yields remain somewhat unoptimised.

<A NAME="RA32203ST-39">39</A> Plante OJ. Palmacci ER. Seeberger PH. Science  2001,  291:  1523