Asymmetric Total Synthesis and Structure Confirmation of (+)-(3E)-Isolaurefucin Methyl Ether

Abstract

-An asymmetric total synthesis and structure confirmation of

Synthesis, Characterization, and Reactivity of Complex Tricyclic Oxonium Ions, Proposed Intermediates in Natural Product Biosynthesis

“…Using chloride in place of bromide anion gave the corresponding ( E )- and ( Z )-chlorofucins 24 in 46% and 63% yields, respectively, along with a trace amount of laurendecumenyne B 21 . , In the other diastereomeric series, treatment of the oxonium ions ent -( E )- and ent -( Z )- 13 ·Al­(pftb) 4 with water gave the corresponding ent -laurefucins ent - 16 in 34% and 51% yields, respectively. , Using acetate anion with ent -( E )- 13 ·Al­(pftb) 4 gave ent -acetyllaurefucin ent - 15 in 30% yield. Both ent -( E )- and ent -( Z )- 13 ·Al­(pftb) 4 were also treated with chloride anion which gave the ent -( E )- and ent -( Z )-neoprelaurefucins ent - 29 in 59 and 73% yields, respectively. , What is clear from these quenching experiments is that all four oxonium ions undergo kinetic quenching at C-10 in keeping with results in related systems. ,,, Additionally, the oxonium ions ( E )- and ( Z )- 20 ·Al­(pftb) 4 undergo a small amount of C-7 quenching analogous to previous work; ,, in keeping with related results, products from quenching of the oxonium ions at C-13 were not observed . The quenching experiments provided the 2,2′-bifuranyl natural products 21 and 22 in low yields.…”

“…The synthetic oxonium ions ent -( E )- and ent -( Z )- 13 ·Al­(pftb) 4 and ( E )- and ( Z )- 20 ·Al­(pftb) 4 were thermally unstable and readily decomposed above −40 °C. Indeed, it was not possible to synthesize the oxonium ion ( E )- 20 ·Al­(pftb) 4 from ( E )-chlorofucin ( E )- 24 as the halide abstraction reaction only occurred above −40 °C (for energy profile for oxonium ion formation, see Figures S33–S35, pp S104–S108) . The thermal instability of a closely related oxonium ion was studied which resulted in the characterization of a clean decomposition pathway (Figure ).…”

“…20 In a similar manner, heating (Z)-chlorofucin (Z)-24 with activated silica gel in chloroform at 80 °C (bath temperature) gave laurendecumenyne B 21 in 73% yield, whilst (E)-chlorofucin (E)-24 gave (E)-laurendecumenyne B (E)-21 which has yet to be isolated from Nature, 20 in 50% yield on exposure to activated silica gel in hexanes at 80 °C (bath temperature). 29 The course of the rearrangement of ent-29 into ent-(Z)-14 at 80 °C (bath temperature) in CDCl3 in the absence of silica gel was readily followed by 1 H NMR (see ESI Figure S59, pS206) which indicated clean and quantitative conversion after 12 days. DFT calculations of transition structures (TSs) helped to explain the observed regioselectivity in the nucleophilic opening of oxonium ions ent-(E)-13 and (E)-20.…”

“…In a related manner, the biosynthesis of numerous halogenated acetogenin natural products from Laurencia species have been proposed to proceed via complex bi- and tricyclic oxonium ions (Figure ). − The existence of these trialkyloxonium ions, as with carbocations in terpene biosynthesis, has been implied from the structural and stereochemical diversity of these natural products and initial biosynthetic studies with isolated enzymes ,, as well as from a number of elegant biomimetic syntheses primarily from Kim, Snyder, and Braddock that involve ring opening/expansions of in situ generated oxonium ions to give a host of structurally diverse Laurencia natural products. − ,− However, no direct evidence for the existence of these trialkyloxonium ions has been forthcoming. Herein we report the synthesis and full characterization (both chemically and computationally) of one family of tricyclic trialkyloxonium ionsamong the most structurally and stereochemically complex oxonium ions characterized to date .…”

Forwards and backwards – synthesis of Laurencia natural products using a biomimetic and retrobiomimetic strategy incorporating structural reassignment of laurefurenynes C–F

“…In the original paper of Jaspars, a plausible biogenesis of the laurefurenynes (((Z/E)-1, (Z/E)-2 and (Z/E)-3) was proposed based on epoxide and/or bromonium ion cyclizations. However, the reassigned structures of laurefurenynes A and B (Z/E)-4 t with a proposed biosynthesis involving the previously characterized tricyclic oxonium ions 7 47 which likely arise via transannular displacement of bromide or chloride from the halofucins 5 and 6 (Scheme 1), 15,48,49 followed by opening of the oxonium ions 7 at C-7 with water and then displacement of the C-12 bromine atom with water with inversion of conguration. 21,22 If it is indeed the case that laurefurenynes A and B (Z/E)-4 are biosynthesized from the halofucins 5 and 6 then it would be reasonable to postulate that laurefurenynes C-F are produced on the same biosynthetic pathway.…”