Fernando Bravo

Biomimetic synthesis via polyepoxide cyclizations

The biomimetic synthesis of trans,syn,trans-fused polycyclic ether natural products involving a cascade of stereospecific and regioselective oxacyclizations of polyepoxide substrates is described as applied to the synthesis of polyoxepane and polypyran structures. In addition, an extension of biomimetic polyene cyclizations to terpenoid natural products is outlined.

Synthesis of Substituted Tetrahydrofuran by Electrophile-Induced Cyclization of 4-Pentene-1,2,3-triols − An Example of 5-exo versus 5-endo Cyclization Governed by the Electrophile

Differently protected 4-pentene-1,2,3-triols 5−8 were obtained from glyceraldehyde and submitted to iodine-based electrophile-induced cyclization to give tetrahydrofuran derivatives 10 and 18, with high chemo-, regio-, and stereoselectivity, through a 5-exo cyclization process. However, when an electrophilic selenium reagent was treated with similar alkene triols 5, 7, and 8, the product depended on the protecting group at the primary hydroxy moiety. Thus, while compounds 5a and 5b, unprotected at the primary hydroxy group, give compounds 26 and 27, and 32 and 33, respectively, through a 5-exo cyclization process, compounds 7 and 8, protected at the primary hydroxy group, give the 5-endo cyclization products 22−25 and 28−31 in good yields. The electrophile-induced cyclization of 4-pentene-1,2,3-triols to give tetrahydrofuran derivatives can be directed towards a 5-exo process by the use of iodine or, when the primary hydroxy group is unprotected, selenium. When the primary hydroxy group is protected, use of selenium results in 5-endo cyclization.

Synthesis of erythro and threo furanoid glycals from 1- and 2-phenylselenenyl-carbohydrate derivatives.

Differently protected erythro and threo furanoid glycals were synthesized by selenoxide elimination when phenyl 1-selenoglycosides were treated in oxidizing conditions (tBuOOH, Ti(O(i)Pr)(4), Et(2)(i)PrN). The phenyl 1-selenoglycosides were obtained from methyl 2-deoxy-D-erythro-pentofuranoside by protection of the primary hydroxyl or both hydroxyls and further reaction with PhSeH in the presence of BF(3).Et(2)O. Erythro and threo furanoid glycals were also prepared by treating 2-deoxy-2-phenylselenenyl-1,4-anhydrocyclitols under similar conditions. The 2-deoxy-2-phenylselenenyl-1,4-anhydrocyclitols were obtained from 4-pentene-1,2,3-triols by a 5-endo selenium electrophilic induced cyclization.

SYNTHESIS OF ERYTHRO AND THREO FURANOID GLYCALS USING 5-ENDO-TRIG SELENOETHERIFICATION AS KEY STEP

Abstract Differently protected erythro and threo furanoid glycals were synthesised from 4-pentene-1,2,3-triol, through selenium induced 5- endo -trig cyclization and selenoxide elimination.

Synthesis of amino-1,4-anhydro-d-pentitols and amino-1,5-anhydro-d-hexitols with the arabino configuration from (R)-glycidol

Abstract 2-Amino-1,4-anhydro-pentitol and 3-amino-1,5-anhydro-4-deoxy-hexitol with the arabino configuration were synthesised from ( R )-glycidol using a metathesis reaction as the key step. The dihydrofuran or dihydropyran products obtained after the metathesis reaction were subjected to epoxidation, epoxide opening with azide anion and finally azide reduction.

Stereoselective synthesis of both enantiomers of 1,4-anhydro-alditols, 1,4-anhydro-2-amino-alditols and d- and l-isonucleosides from 2,3-O-isopropylidene-d-glyceraldehyde using iodine-induced cyclization as the key step

Abstract We have stereoselectively prepared the enantiomeric 1,4-anhydro-alditols (−)- 15 and (+)- 15 , 1,4-anhydro-2-amino-alditols (−)- 19 and (+)- 19 , and isonucleosides (−)- 22 , (+)- 22 and 25 , from 2,3- O -isopropylidene- d -glyceraldehyde. The key step was the iodine-induced cyclization of 4-pentene-1,2,3-triols 2 and 3 to give, respectively, the tetrahydrofuran derivatives 4 and 5 . In these compounds we have optimized the substitution of iodine for oxygen-bearing groups. Results were best when we used potassium superoxide as a nucleophile.

Stereoselective synthesis of L-isonucleosides

l-Isonucleosides 17 and 19 were stereoselectively synthesised from (S)-glycidol by two different procedures. The key step was the synthesis of a chiral dihydrofuran which was carried out by oxidation/elimination of 8 and by ring-closing metathesis of diene 10. The procedure can be applied to the synthesis of both enantiomers.