Synthesis of Phytuberin. 4-endo-tet Acid-Catalyzed Cyclization of α-Hydroxy Epoxides

Abstract

The total synthesis of phytuberin, a phytoalexin of the Solanum genus, from (-)-alpha-santonin is reported. The key steps include (a) reductive cleavage of the C-O bond of the gamma-lactone with concomitant protection of the C1 double bond, (b) Sharpless stereocontrolled hydroxy-assisted epoxidation of allylic alcohol 6 and simultaneous deprotection of the C1 double bond, (c) a rare 4-endo-tet acid-catalyzed cyclization of an alpha-hydroxy epoxide, and (d) an unprecedented 4-exo selenocyclization of a homoallylic alcohol.

Apparent Alkyl Transfer and Phenazine Formation via an Aryne Intermediate

“…Specifically, Hase has performed an ab initio (HF/3-21+G*) trajectory study of the S N 2 reaction of Cl – + CH 3 Cl at a reagent relative translational energy of 100 kcal/mol and observed the expected backside attack but no frontside attack and suggested that extensive electrophile vibrational energy would be required for frontside attack. Furthermore, reported 5- endo-tet processes are ambiguously categorized since they involve 3-membered ring (generally epoxide) openings under acidic conditions with significant carbocation character and hence are more appropriately categorized as (allowed) 5- exo-trig reactions. Indeed, Baldwin noted that three-membered ring-openings lie between tetrahedral and trigonal systems .…”

Eudesmane sesquiterpenoids from the Asteraceae family

“…425 An easy route to racemic 11-hydroxyeudesmanolides, such as decipienin A, has been described, 472 and short syntheses of dehydroisoerivanin, isoerivanin, ludovicin C and 1a,3a-dihydroxyarbusculin B have been described. 473 (−)-a-Santonin has been used as starting material in the synthesis of phytuberin, 474 and other studies towards the biomimetic synthesis of these sesquitepene lactones have been described. 475 Syntheses of (−)-isobaimuxinol and (−)-baimuxinol have been reported, 476,477 and cytotoxic a-aminomethyl-substituted eudesmanolides have been prepared by stereoselective Michael-type addition of amines to alantolactone and isoalantolactone.…”

Total Syntheses of the Monoterpene Indole Alkaloids (±)-Alstilobanine A and E and (±)-Angustilodine

“…An attempt was then made to effect a Mitsunobu cyclization of this triol to generate the oxepane . Treatment of 65 with triphenylphosphine and DIAD (1 equiv) in benzene at room temperature, however, did not afford any of the desired oxepane, but rather gave a chromatographically separable mixture of the tetrahydrofuranyl ether 67 (51%) and oxetane 68 (23%). Interestingly, using an excess of DIAD (5 equivalents) under the same reaction conditions produced the cyclopropane tetrahydropyranyl ether 66 in high yield .…”