RCM-Based Synthesis of a Variety of β-C-Glycosides and Their in Vitro Anti-Solid Tumor Activity

Abstract

The synthesis of a number of biologically relevant C-glycosides has been carried out through the use of an esterification-ring-closing metathesis (RCM) strategy. The required acid precursors were readily prepared via a number of standard chemical transformations followed by dehydrative coupling of these acids with several olefin alcohols 1 to yield the precursor esters 3 in excellent yield. Methylenation of the esters 3 was followed by RCM and in situ hydroboration-oxidation of the formed glycals to furnish the protected beta-C-glycosides 6 in good overall yield. Several examples were converted to the corresponding C-glycoglycerolipids 17 and subsequently screened against solid-tumor cell lines for in vitro differential cytotoxicity.

Transition metals in organic synthesis: Highlights for the year 2005

“…Synthetic targets include, the heterocyclic core of GE 2270 [34], peridinin [35], pyrones isolated from placobranchus ocellatus [36], terpenepolyketide natural products [37], dihydroxerulic and xerulinic acid [38], bipinnatin J [39], elipticine [40], (+)-7-deoxytrans-dihydronarciclasine [41], gambierol [42], taiwaniaquinol [43], (−)-scabronine G [44], garsubellin A [45], piericidin A1 and B1 [46], lucilactaene [47], fostriecin [48], lupine alkaloids [49], ␤-C-glycosides [50], (+)-crocacin D [51], lobatamide analogs [52], epoxyquinoid compounds [53,54], (+)-SCH 351448 [55], 3-methyl-2,5-dihydro-1-benzoxepin carboxylic acids [56], (+)-ochromycinone and (+)-rubiginone B 2 [57], EI-1941-1 and EI-1941-2 [58], mycothiazole [59], 6 -epiperidinin [60], aureothin and N-acylaureothamine [61], cyercene A and placidenes [62], herbindole B [63], (+)-tubelactomicin A [64], saudin [65], peroxyacarnoates A and D [66], aureothin, N-acetylaureothamine, aureonitrile [67], elysiapyrones [68], altromycin B [69], (+)-phorboxazole A and analogues [70,71], (−)-SNF4435 C and (+)-SNF4435 D [72], A2E [73], paracentrone [74]<...>…”

“…(50)) [489]. (50) Palladium-catalyzed oxidative addition to 2-iodobenzenamine derivatives followed by alkyne insertion and intramolecular amino-palladation producing indoles were used to prepare a variety of alkaloids [370,490,491,373]. Palladium catalyzed the reaction of 2-iodopyrroles with 4-ynoic acids (Eq.…”

Gram‐Scale Preparation of a p‐(C‐Glucopyranosyl)‐L‐phenylalanine Derivative by a Negishi Cross‐Coupling Reaction

“…The functionalization of the double bond of the coupling products in order to gain access to the pyranosyl ring might be achieved either by hydroboration followed by oxidation [15] or by dihydroxylation followed by reduction. [16] Compound 4b was chosen as it was obtained in a better yield and it bears the most-stable protective groups.…”

“…[15] Thus, hydroboration of 8 with an excess of BH 3 ·THF, followed by oxidative quenching (H 2 O 2 , NaOH) of the organoborane and then acetylation of the free hydroxy group, afforded the p-(C-glucopyranosyl)phenylalanine derivative 6 in 66 % yield over two steps (Scheme 4). The β configuration of this new C-glycoside was assigned by the coupling constant of 9.6 Hz between the H 1 and H 2 protons of the carbohydrate ring.…”

Synthesis of 7‐Aza‐ and 7‐Thiasphingosines, and Evaluation of Their Interaction with Sphingosine Kinases and with T‐Cells

“…2955w, 2917s, 2850s, 1615w, 1579w, 1467w, 1431w, 1337w, 1101w, 1052m, 1038m, 1021m, 994m, 967m, 957m, 889w, 812w, 720w, 646w. (E)-2-Azido-2,4,5,6-tetradeoxy-1,3-bis-O-(methoxybenzyl)-6-(undecylsulfonyl)-d-erythro-hex-4-enitol (20). A soln.…”