Stilbenophane Analogues of Deoxycombretastatin A-4

Abstract

A new family of polyoxygenated stilbenophanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. By means of the McMurry olefination process, compounds derived from diethyleneglycol and 1,6-hexanediol were obtained, whereas Grubbs' catalyst failed in producing the ring-closing metathesis to this kind of macrocyclic products.

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

“…Although the idea of a macrocyclic analog of CA-4 is quite attractive, the resulting compounds ( e.g. , 74, 75 ) did not lead to biological activity on tubulin, precluding their anticancer applications (73). …”

Transition metals in organic synthesis: Highlights for the year 2005

“…(221)) [1117,1118], hybrids of d-galactose with 1-deoxynojirimycin analogs [1119], the tetracyclic core of tetrapentalones [1120], 1-epi aglycon of cripowellins A and B [445], gambieric acid [1121], aspercyclide C [524], radicicol and pochonin C [1122], trachelanthamidine [1123], heliannuols G and H [652], (−)-Geismann-Waiss lactone [1124], tuberostemonines [688], (−)-kendomycin [1125], pochonin D [1126], (−)-223A [1127], coleophomones B-D [1128], brevetoxin B [130], garsubellin A [45], fostriecin [48], 11-acetoxy-4-deoxyasbestin D [1129], (+)-cyclophellitol [1130], ␤-C-glycosides [50], zoapatanol [247], deoxymannojirimycin and swainsonine [1131], valienamine [1132], A 3 adenosine recetor agonists [1133], vincantril [810], (−)-perhydrohistrionicotoxin [1134], annonaceous acetogenins [1135], deoxycombrestatin A-4 analogs [1136], (+)-lentiginosine and analogs [1137], N-malayamycin A [1138], (−)-salicylhalamides A and B [938], oxytocin analogs [1139], steroid-like compounds [440], (−)-isoprelaurefucin [338], halichondrin B [1140], (−)-microcarpalide and (+)-lethaloxin [1141,1142], anamarine …”

Synthesis and Conformational Analysis of Macrocyclic Dihydroxystilbenes Linked between thepara–paraPositions

“…As described, when the McMurry reaction is carried under reflux, the diols are partly reduced to stilbenophanes 20a. The olefins are not formed at room temperature and mixtures of isomeric glycols are produced in good yields, although they were strongly retained by the silica gel, thus lowering the yields of the isolated products.…”

“…Whereas small para ‐cyclophanes (e.g., [2.2]paracyclophane) are highly constrained molecules, the ring strain of [2.7]‐ or [2.8]paracyclophanes, such as those described herein, should be far less important. The interference of the methoxy groups on the aromatic ring with the linker and the conformational preferences of the pinacol subunit must both contribute to the increased rotational barrier of the phenyl rings, as the analogue stilbenophanes do not show such behavior 20a. The same applies for the trans isomers.…”

“…4‐[6‐(4‐Formylphenoxy)hexoxy]‐3,5‐dimethoxybenzaldehyde (2 b) :20a Obtained as an oily compound in 62 % yield. M.p (hexane/Et 2 O) 275 °C.…”