1413282-41-3

Upstream product

• 100-58-3 phenylmagnesium bromide 
• 582-52-5 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose 
• 53167-11-6 1,2-O-isopropylidene-α-D-xylo-pentodialdo-1,4-furanose 
• 18439-34-4 (3aR,5R,6S,6aR)-5-((S)-hydroxy(phenyl)methyl)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxole-6-ol 
• 1413282-39-9 3,5-O-carbonyl-1,2-O-isopropylidene-5-C-phenyl-α-D-glucopentofuranose 
• 18439-35-5 (3aR,5R,6S,6aR)-5-((R)-hydroxy(phenyl)methyl)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxole-6-ol 

Downstream Products

• 918906-87-3 8-epi-crassalactone D 
• 1190851-29-6 4-epi-(+)-crassalactone D 

Relevant academic research and scientific papers

Asymmetric synthesis and biological evaluation of (+)-cardiobutanolide, (?)-3-deoxycardiobutanolide and analogues as antiproliferative agents

Two natural products, (+)-cardiobutanolide and (?)-3-deoxycardiobutanolide, as well as five new analogues, were synthesized in several steps that included zinc-mediated THF ring opening, subsequent stereoselective olefination, and final Sharpless asymmetric dihydroxylation. In vitro antitumour activities of these compounds were evaluated against a panel of eight human tumour cell lines and one normal cell line. Some of compounds displayed powerful effects against tumour cells, but none of them were active toward normal cells. A SAR study revealed that the change of configuration at the C-6 and C-7 position of (+)-cardiobutanolide decreases antitumour activity of analogues. It also appears that the presence of a hydroxyl group at the C-3 position increases the activity of this type of lactones. A comparison of activities of conformationally rigid lactone goniofufurone with that of more flexible cardiobutanolide and 3-deoxycardiobutanolide indicates that steric flexibility has a positive effect on cytotoxicity. It was also confirmed that removal of the phenyl group may result in analogues of higher activity. Flow cytometry analysis revealed that the synthesized compounds did not induce apoptosis and necrosis of K562 cells. However, Western blot analysis showed that all compounds but one had an increased Bax/Bcl-2 protein expression ratio.

Synthesis and in?vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives

Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi-crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been synthesized starting from D-glucose. The key step of the synthesis is a new one-pot sequence that commenced with a Z-selective Wittig olefination of suitably functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)-triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the corresponding 4-epimers (2 or 4, respectively). A number of 6-O-cinnamoyl derivatives of styryl lactones 1–4 have been prepared, bearing electron donating or electron withdrawing functionalities in the C-4 position of cinnamic acid residue. The synthesized products were evaluated for their in?vitro antiproliferative activity against selected human tumour cell lines, whereupon very potent cytotoxicities have been recorded in many cases. SAR analysis indicated some important structural features responsible for biological activity, such as stereochemistry at the C-4 and C-7 positions, as well as the nature of a substituent at the C-4 position in the aromatic ring of cinnamoate moiety. Flow cytometry and Western blot analysis data gave insight in the mechanism underlying antiproliferative effects of the synthesized compounds.

Synthesis and antiproliferative activity of goniobutenolides A and B, 5-halogenated crassalactone D derivatives and the corresponding 7-epimers

A new synthesis of goniobutenolides A (1) and B (2) and the corresponding 7-epimers has been achieved starting from diacetone d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with Z-selective Wittig (or Horner-Wadsworth-Emmons) olefination, followed by successive γ-lactonisation and β-elimination. The above-mentioned unsaturated lactones were then converted to the corresponding 5-halogenated crassalactone D derivatives by using the appropriate haloetherification protocol. The most of synthesized compounds exhibited potent cytotoxic activities against a panel of tumour cell lines. The main structural features responsible for their antitumour potency have been revealed by means of SAR analysis. Flow cytometry data suggested that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of semi-quantitative Western blot analysis indicate that the most of synthesized compounds induce apoptosis in a caspase-dependent manner.

Divergent synthesis of cytotoxic styryl lactones related to goniobutenolides A and B, and to crassalactone D

Goniobutenolides A (1) and B (2), crassalactone D (3), 4-epi-crassalactone D (4), and the corresponding 7-epimers have been synthesized starting from d-glucose. The key step in the synthesis of 1 and 2 is a new one-pot sequence comprised of a Z-selective Wittig olefination/lactonization/β-elimination. Preparation of 3 and 4 included the final 5-endo-trig spirocyclization of 1 and 2. The synthesized products were evaluated for their in vitro antiproliferative activity against selected tumor cell lines.