Total Synthesis of Mallotusinin

Abstract

The total synthesis of mallotusinin, which bears a tetrahydroxydibenzofuranoyl (THDBF) bridge between the 2oxygen and 4-oxygeno fg lucose on corilaginw ith a3 ,6-O-(R)-hexahydroxydiphenoyl (HHDP) bridge, is described. The key features of the total synthesis are:1)improvements of our previously reported method to synthesize corilagin; 2) establishment of the THDBF skeleton via an unusuali ntramolecular S N Ar reactionofanHHDP analogue, and 3) the application of at wo-step bislactonization strategy for aH HDP bridge construction into the 2,4-O-THDBF bridge. Oxidative phenolc oupling of 1,2,4-orthoacetyl-3,6-di-(4-O-benzylgalloyl)-ad -glucopyranose and the orthoester cleavage of the couplingp roduct without the pyranose-furanose ring transformation are keyr eactions for the improved synthesis of corilagin,w hich enabled the adequate supply of ac orilagin precursor that was required to develop the mallotusinin synthesis. These established methods are expected to help develop the synthesis of other ellagitannins with ab ridge between the two oxygens of corilagin.

The beauty of biocatalysis: sustainable synthesis of ingredients in cosmetics

“…115,119–122 More recently total syntheses of some ellagitannins have been achieved chemically. 123–127…”

A generally applicable quantitative reactivity model for nucleophilic aromatic substitution built from simple descriptors

“…SNAr is one of the most important and well-studied transformations in organic synthesis. [26][27][28][29] It is extensively used in total synthesis of natural products, [30][31][32][33][34][35][36][37] medicinal chemistry and agrochemistry, [38][39][40][41][42][43] and manufacturing of active pharmaceutical and agrochemical ingredients. [44][45][46][47][48] For example, SNAr reactions are particularly powerful for the synthesis and functionalization of N-heterocycles, which are among the most ubiquitous structural components in active pharmaceutical ingredients.…”

Seven-Step Stereodivergent Total Syntheses of Punicafolin and Macaranganin

“…The strategy was successfully applied to the first total synthesis of a 1 C 4 / B -ellagitannin, corilagin, in 2008 (Scheme b, route A) . Recently, Ikeuchi, Yamada, and co-workers reported an improved synthesis of corilagin via a conformationally fixed intermediate (Scheme b, route B) . In these precedents, use of a ring-opened pyranose derivative or a conformationally fixed pyranose derivative seemed essential for the construction of the 3,6-HHDP group.…”

“…8 Recently, Ikeuchi, Yamada, and co-workers reported an improved synthesis of corilagin via a conformationally fixed intermediate (Scheme 1b, route B). 9 In these precedents, use of a ring-opened pyranose derivative or a conformationally fixed pyranose derivative seemed essential for the construction of the 3,6-HHDP group. For straightforward total synthesis, direct formation of the 3,6-HHDP group from a stable chair 4 C 1 conformation with all equatorial substituents seems to be more desirable.…”

“…The preference of the (R)-3,6-HHDP bridge with the glucose core was compatible with the observation of exclusive formation of the (R)-3,6-HHDP-bridged glucose derivatives during the total synthesis of corilagin and mallotusinin. 8,9 Thermal equilibrium between 16 and 17 was also examined. Treatment of 16 in d 6 -DMSO (2 mg/mL) at 130 °C for 30 min gave >99% recovery without any formation of 17.…”