TY - JOUR
T1 - Synthesis of 2,6-dioxatricyclo[3.3.1.03,7]nonanes by intramolecular haloetherification and/or transannular hydroxycyclization of alkenes in [4+3]-cycloadducts
AU - Montana, A M
AU - Barcia, J A
AU - Kociok-Kohn, Gabriele
AU - Font-Bardia, M
PY - 2009/7/4
Y1 - 2009/7/4
N2 - The synthesis of new difunctionalized 2,6-dioxatricyclo[3.3.1.03,7]nonanes is described. This type of structure is an interesting synthetic building block for potential bioactive molecules and it was prepared from 8-oxabicyclo[3.2.1]oct-6-en-3-one having a NHBoc function on C-1. This precursor was obtained by a [4+3] cycloaddition reaction of 2-tert-butoxycarbonylaminofuran and the oxyallyl cation generated in situ from 2,4-dibromo-3-pentanone. Reduction of the carbonyl group at C-3 was accomplished in high yield and stereoselective manner to afford the corresponding axial alcohol at C-3 as a major product. Further intramolecular haloetherification of this type of alcohols with NBS and I(py)2BF(4) led to the corresponding bromo and iodo-derivatives at C-8 of the 2,6-dioxatricyclo[3.3.4.0(3,7)]nonane framework, in high yield. Epoxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-ol followed by treatment with NaCN, NaN3, and/or NaOH in MeOH afforded 8-hydroxy-2,6-dioxatricyclo[3.3.1.03,7]nonanes in high yield via a transannular hydroxycyclization mediated by a base and through an alkoxide intermediate. The new 2,6-dioxatricyclo[3.3.1.03,7]nonanes were tested for biological activity against HIV-1 virus and MT-4 lymphoid cell line, showing a low anti-HIV activity and a high degree of cytotoxicity.
AB - The synthesis of new difunctionalized 2,6-dioxatricyclo[3.3.1.03,7]nonanes is described. This type of structure is an interesting synthetic building block for potential bioactive molecules and it was prepared from 8-oxabicyclo[3.2.1]oct-6-en-3-one having a NHBoc function on C-1. This precursor was obtained by a [4+3] cycloaddition reaction of 2-tert-butoxycarbonylaminofuran and the oxyallyl cation generated in situ from 2,4-dibromo-3-pentanone. Reduction of the carbonyl group at C-3 was accomplished in high yield and stereoselective manner to afford the corresponding axial alcohol at C-3 as a major product. Further intramolecular haloetherification of this type of alcohols with NBS and I(py)2BF(4) led to the corresponding bromo and iodo-derivatives at C-8 of the 2,6-dioxatricyclo[3.3.4.0(3,7)]nonane framework, in high yield. Epoxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-ol followed by treatment with NaCN, NaN3, and/or NaOH in MeOH afforded 8-hydroxy-2,6-dioxatricyclo[3.3.1.03,7]nonanes in high yield via a transannular hydroxycyclization mediated by a base and through an alkoxide intermediate. The new 2,6-dioxatricyclo[3.3.1.03,7]nonanes were tested for biological activity against HIV-1 virus and MT-4 lymphoid cell line, showing a low anti-HIV activity and a high degree of cytotoxicity.
UR - http://www.scopus.com/inward/record.url?scp=66149098538&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.tet.2009.04.076
U2 - 10.1016/j.tet.2009.04.076
DO - 10.1016/j.tet.2009.04.076
M3 - Article
SN - 0040-4020
VL - 65
SP - 5308
EP - 5321
JO - Tetrahedron
JF - Tetrahedron
IS - 27
ER -