Syntheses of Guanidinoglycosides with the Inventive use of Mitsunobu Conditions­ and 1,8-Diazabicyclo[5.4.0]undec-7-ene

Abstract

A series of novel guanidinoglycosides was successfully synthesized. This was accomplished with the use of Mitsunobu conditions as a strategy to convert the glycopyranose anomeric hydroxy group to give the corresponding substituted masked guanidines in high yields. Subsequent deprotection and coupling with Fmoc protected β-amino acid, afforded a series of N,N′-substituted-methylisothioureas. Cleavage of Fmoc followed by concomitant cyclization was achieved with a catalytic amount of DBU to give the guanidinoglycosides.

guanidine - glycosides - Mitsunobu reaction - coupling - cyclization

References

<A NAME="RF05902SS-1">1</A>

First and second authors contributed equally to this work.

<A NAME="RF05902SS-2A">2a</A> Lemieux RU. Wolfrom ML. Adv. Carbohydr. Chem.  1948,  3:  337 

<A NAME="RF05902SS-2B">2b</A> Maurin M. Raoult D. Antimicrob. Agents Chemother.  2001,  45:  2977 

<A NAME="RF05902SS-3">3</A> Delaware DL. Sharma MS. Iyengar BS. Remers WA. J. Antibiot.  1986,  39:  251 

<A NAME="RF05902SS-4">4</A> Cotner ES. Smith PJ. J. Org. Chem.  1998,  63:  1737 

<A NAME="RF05902SS-5">5</A> Reitz AB. Tuman RW. Marchione CS. Jordan AD. Bowden CR. Maryanoff BE. J. Med. Chem.  1989,  32:  2110 

<A NAME="RF05902SS-6A">6a</A> Feichtinger K. Zapf C. Sings HL. Goodman M. J. Org. Chem.  1998,  63:  3804 

<A NAME="RF05902SS-6B">6b</A> Feichtinger K. Sings HL. Baker TJ. Matthews K. Goodman M. J. Org. Chem.  1998,  63:  8432 

<A NAME="RF05902SS-7">7</A> Baker TJ. Luedtke NW. Tor Y. Goodman M. J. Org. Chem.  2000,  65:  9054 

<A NAME="RF05902SS-8">8</A> Lin P. Lee CL. Sim MM. J. Org. Chem.  2001,  66:  8243 

<A NAME="RF05902SS-9A">9a</A> Gololobov YG. Zhmurova IN. Kasukhin LF. Tetrahedron  1981,  37:  437 

<A NAME="RF05902SS-9B">9b</A> Molina P. Vilaplana MJ. Synthesis  1994,  1197 

<A NAME="RF05902SS-10A">10a</A> Hughes DL. Org. Prep. Proced. Int.  1996,  28:  127 

<A NAME="RF05902SS-10B">10b</A> Mitsunobu O. Synthesis  1981,  1 

<A NAME="RF05902SS-11A">11a</A> Dodd DS. Wallace OB. Tetrahedron Lett.  1998,  39:  5701 

<A NAME="RF05902SS-11B">11b</A> Kim H. Mathew F. Ogbu C. Synlett  1999,  2:  193 

<A NAME="RF05902SS-11C">11c</A> Dodd DS. Kozikowski AP. Tetrahedron Lett.  1994,  35:  977 

<A NAME="RF05902SS-12">12</A>

To further prove the existence of rotomers, Boc-protection of 2 was carried out using Boc₂O and DMAP in CH₂Cl₂. Both 2a and 2b yielded only their respective α rotomers.

<A NAME="RF05902SS-13A">13a</A> Bu X. Xie G. Law CW. Guo Z. Tetrahedron Lett.  2002,  43:  2419 

<A NAME="RF05902SS-13B">13b</A> Sheppeck JE. Kar H. Hong H. Tetrahedron Lett.  2000,  41:  5329 

<A NAME="RF05902SS-13C">13c</A> Metcalf CA. Vu CB. Sundaramoorthi R. Jacobsen VA. Laborde EA. Green J. Green Y. Macek KJ. Merry TJ. Pradeepan SG. Uesugi M. Varkhedkar VM. Holt DA. Tetrahedron Lett.  1998,  39:  3435 

<A NAME="RF05902SS-13D">13d</A> Wade JD. Bedford J. Sheppard RC. Tregear GW. Pept. Res.  1991,  4:  194 

<A NAME="RF05902SS-14A">14a</A> Ouyang X. Kiselyov AS. Tetrahedron  1999,  55:  8295 

<A NAME="RF05902SS-14B">14b</A> Mori Y. Yaegashi K. Furukawa H. Tetrahedron Lett.  1999,  40:  7239 

<A NAME="RF05902SS-14C">14c</A> Magri NF. Kingston DGI. J. Nat. Prod.  1988,  51:  298 

<A NAME="RF05902SS-14D">14d</A> Roush WR. Follows BC. Tetrahedron Lett.  1994,  28:  4935