Total Synthesis of Phorboxazole A via de Novo Oxazole Formation: Strategy and Component Assembly

Abstract

The phorboxazole natural products are among the most potent inhibitors of cancer cell division, but they are essentially unavailable from natural sources at present. Laboratory syntheses based upon tri-component fragment coupling strategies have been developed that provide phorboxazole A and analogues in a reliable manner and with unprecedented efficiency. This has been orchestrated to occur via the sequential or simultaneous formation of both of the natural product's oxazole moieties from two serine-derived amides, involving oxidation-cyclodehydrations. The optimized preparation of three pre-assembled components, representing carbons 3-17, 18-30, and 31-46, has been developed. This article details the design and syntheses of these three essential building blocks. The convergent coupling approach is designed to facilitate the incorporation of structural changes within each component to generate unnatural analogues, targeting those with enhanced therapeutic potential and efficacy.

Augmenting Photoinduced Charge Transport in a Single‐Component Gel System: Controlled In Situ Gel–Crystal Transformation at Room Temperature

“…Although, af ew literature reports have addressed the gel to crystal transition for other organic systems, [13][14][15][16][17] pre-programming of am olecular engineering to afford this phase change from an assembly composed of single molecular components, undera mbient conditions, is an arduoust ask. This is because the phase change, in almosta ll cases,i sa ccompanied by an externals timuli/additive.…”

Efficient and regioselective synthesis of γ-lactone glycosides through a novel debenzylative cyclization reaction

“…The aqueous phase was extracted with Et2O and the combined organic layer were washed with brine (2 times), dried over MgSO4 and concentrated under reduced pressure to afford 2,3,4,5-tetra-O-benzyl-aldehydo-D-arabinose. 9 The product was engaged in the next step without further purification. 2,3,4,5-Tetra-O-benzyl-aldehydo-D-arabinose (0.604 mmol) was dissolved in a mixture of dichloromethane/water (2/1, 3.6 ml) and cooled to 0 °C.…”

Lewis Base–Brønsted Acid–Enzyme Catalysis in Enantioselective Multistep One‐Pot Syntheses

“…[1][2][3] In recent advances it was demonstrated how elegant advantages of the individual catalytic steps can be exploited without the need for extensive purification, long hands-on times or large amounts of solvents.S ometimes combined approaches even turn out to be superior to individual steps by providing higher overall yields or avoiding the direct handling of certain troublesome materials.N aturally,h owever,t hose potentially fruitful endeavors bear challenges in orchestrating as uitable arrangement of reagents,catalysts and conditions to prevent not only undesired side reactions or decomposition of compounds,but also especially the inactivation of catalysts. [4][5][6][7][8][9][10][11][12][13] Thefocus of the present study is on a-methylated ketones 1 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and diols 2, [32][33][34][35][36][37][38][39][40] which are used extensively in natural product syntheses.O ver decades,t hey not only proved indispensable for finding and examining new pharmacologically active agents,but also for elucidating the mode of action of established blockbusters ranking among the most important drugs by sale.…”