ChemInform Abstract: A Synthetic Approach to Rocaglamide via Reductive Cyclization of δ‐Keto Nitriles.

Abstract

ChemInform Abstract Starting with the benzofuranone (I), the nitrile (II) is prepared, which undergoes cyclization upon treatment with samarium diiodide, forming the tricyclic ketone (IV) as the main product. This is converted to the diastereomer (X) of the anticancer agent rocaglamide via the thiolo ester (VII). An alternative route to (X) also involving a SmI2-induced ring closure of a cyanobenzofuranone is described in the original paper.

Design and Characterization of Optimized Adenosine A2A/A1 Receptor Antagonists for the Treatment of Parkinson's Disease

“…The synthesis of compounds 4−13 started with the commercially available 6-methylindanone 15, which was deprotonated with NaHMDS and reacted with CS 2 followed by MeI to afford the dithioketenacetal 16 (Scheme 2). 28,36 Compound 16 reacts with guanidine to form an intermediate amino pyrimidine, not shown, that is then oxidized to the corresponding ketone by passing air through the solution to Table 1. Human Functional A 2A and A 1 in Vitro Activity and Reversal of Neuroleptic-Induced Catalepsy in Mice a The in vivo activity of reversing haloperidol-induced catalepsy is reported as an ED 50 , % reversal of at a single dose, or not active at a single dose.…”

“…The synthesis of compounds 4 – 13 started with the commercially available 6-methylindanone 15 , which was deprotonated with NaHMDS and reacted with CS 2 followed by MeI to afford the dithioketenacetal 16 (Scheme ). , Compound 16 reacts with guanidine to form an intermediate amino pyrimidine, not shown, that is then oxidized to the corresponding ketone by passing air through the solution to give 17 . The amino pyrimidine was protected using excess (Boc) 2 O and 4-(dimethylamino)pyridine (DMAP) to give 18 .…”

Chemistry and Biology of Rocaglamides (= Flavaglines) and Related Derivatives from Aglaia Species (Meliaceae)

“…15) (120). Like Taylor ’s approach, the investigators began their synthesis with the known intermediate 126 .…”

Progress in the Total Synthesis of Rocaglamide

“…An earlier attempt to synthesize rocaglamide (1) by Kraus and Sy in 1989 resulted in the synthesis of the di-epi analog of rocaglamide (6) , as shown in Scheme 2 [16]. Michael addition of benzofuranone 2 to cinnamonitrile 3 gave keto-nitrile 4 in a 5 : 1 diastereomeric ratio.…”

“…Michael addition of the benzofuranone 2 to cinnamaldehyde (11) , followed by SmI 2 -mediated intramolecular pinacolic coupling of ketoaldehyde 12 , gave diols 13a and 13b , which could be separated by chromatography. Swern oxidation of diol 13b yielded ketone 14 , which was converted into β -keto ester 15 using the CS 2 -based procedure as utilized by Kraus and Sy [16]. The keto ester 15 was then converted into ketoamide 16 , followed by a stereoselective reduction with Me 4 NBH(OAc) 3 to give (±)-rocaglamide (1) .…”