The application of vinylogous iminium salt derivatives to efficient formal syntheses of the marine alkaloids lamellarin G trimethyl ether and ningalin B

Abstract

Studies directed at the synthesis of lamellarin G trimethyl ether and ningalin B via vinylogous iminium salt derivatives are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 1,2,3,4-tetrasubstituted pyrrole from a vinylogous iminium salt or vinylogous iminium salt derivative. Subsequent transformations of these highly substituted pyrroles lead to efficient and regiocontrolled formal syntheses of the respective pyrrole containing natural products.

The application of formyl group activation of bromopyrrole esters to formal syntheses of lycogarubin C, permethyl storniamide A and lamellarin G trimethyl ether

“…Lamellarin G trimethyl ether (6) is the substance often used as a synthetic target for proof of concept for new synthetic methods and approaches. We have previously reported 24 a vinamidinium salt based approach to this important target and we decided to use our new synthetic methodology (Scheme 5) for the preparation of a key pyrrole intermediate (28), which we previously described 24 in our formal synthesis of lamellarin G trimethyl ether (6).…”

“…The resulting product is iodinated at C-3 (27) and this material undergoes cross-coupling to produce a tetrasubstituted pyrrole (28), which we previously prepared 24 via the vinamidinium salt route and was fully characterized. The spectral properties for the product (28) of our new methodology were identical to those we reported earlier.…”

“…After cooling to room temperature, the reaction mixture was filtered through a short plug of silica gel and was subsequently washed with ethyl acetate (2×30 mL) and the combined organic phases were concentrated in vacuo to yield a dark solid. The crude material was purified via flash chromatography on a Biotage Isolera system in which case a light colored solid (0.300 g, 70% yield) was obtained, which have previously prepared 24 and characterized via a different route: 1 H NMR (CDCl 3 ) δ 9.79 (s, 1H), 7.05 (dd, J = 3.0 Hz, J = 9.0 Hz, 1H), 7.02 (d, J = 3.0 Hz, 1H), 7.00 (d, J = 1.5 Hz, 1H), 6.97(d, J = 9.0 Hz, 1H), 4.42 (q, J = 6.0 Hz, 2H), 3.95 (broad s, 6H) and 1.42(t, J = 6.0 Hz, 3H).…”

“…After removing the drying agent by filtration and concentration in vacuo a dark solid product was obtained. The crude material was purified via flash chromatography on a Biotage Isolera system in which case an orange solid (0.162 g, 70% yield) was obtained, which we have previously prepared 24 and characterized via a different route: 1 H NMR (DMSO-d 6 ) δ 9.45 (s, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 2.1 Hz, 1H), 6.92 (dd, J = 2.1 Hz, J = 8.4 Hz, 1H), 4.32 (q, J = 7.2 Hz, 2H), 3.81 (s, 3H), 3.77 (s, 3H) and 1.33 (t, J = 7.2 Hz, 3H).…”

Synthesis of 2,2'-Dipyrryl Ketones from Pyrrole-2-carboxylic Acids with Trifluoroacetic Anhydride

“…The hydrolysis was quite sluggish, to our surprise, and actually the reaction was not completed even after 3 days under the influence of KOH (10 equiv) in refluxing aqueous dioxane. 9 After much trials we found that the hydrolysis was conducted efficiently in a mixed solvent, THF/MeOH/H 2 O (2:2:1), at 50 o C in the presence of an excess amount of KOH (10 equiv) within shorter time (36-42 h).…”