Allenes. Part XIX. Synthesis of (±)-hypoglycin A and configuration of the natural isomer

Abstract

The synthesis of hypoglycin A by way of the allenic intermediate, diethyl 1 -formylaminopenta-3,4-diene-l,1 -dicarboxylate, by Sirnrnons-Smith methylation, is described. Model experiments with ethyl buta-2.3-dienoate and diethyl allyl(formylamino)malonate gave ethyl methylenecyclopropanecarboxylate and, after hydrolysis and decarboxylation, 2-amino-3-cyclopropylpropionic acid. Degradation of hypoglycin A to (+)-3-methylpentanoic acid of known (S)-configuration establishes the configuration as (+)-(2s: 4s) -2-amino-4,5-methanohex-5-enoic acid.known to add to allenes at the more highly substituted double bond.13 The Simmons-Smith reaction is somewhat temperamental and requires an active zinc-copper couple and strictly anhydrous conditions for reasonable

Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 2. 3,4- and 4,5-Methanoamino Acids

“…Hydrolysis and decarboxylation gave the (R*,R*)-diastereomer of hypoglycine A 436, which was wrongly considered to have the same configuration as the natural product (Scheme 77, eq 2). 285,286 Another synthesis of racemic hypoglycine A started with the titanium-catalyzed hydroxymethylcyclopropanation of vinylacetaldehyde diethyl acetal (445) with isopropylmagnesium bromide in the presence of ethyl acetate. The thus obtained cyclopropanol 446 was tosylated and the tosylate eliminated to the methylenecyclopropane derivative 447.…”

“…Simmons−Smith cyclopropanation of 444 occurred regioselectively at the more highly substituted double bond, affording 442 . Hydrolysis and decarboxylation gave the ( R *, R *)-diastereomer of hypoglycine A 436 , which was wrongly considered to have the same configuration as the natural product (Scheme , eq 2). , …”

The synthesis of a cyclopropane amino acid, trans-α-(carboxycyclopropyl)glycine, found in ackee seed

“…The combined organic layers were washed with water, dried over anhydrous potassium carbonate, evaporated, and distilled to give ethyl (E)-4,4diethoxybut-2-enoate (1) (7. (2).-(a) A mixture of freshly distilled 2-furaldehyde (125 g), absolute ethanol (900 ml), and eosin (2 g), using the literature method except that a mediumpressure lamp (Hanovia 100-W) was used, gave (Z)-3-formylpropenoic acid pseudo-ester (2) (99 g, 60%), b.p. 115-1 18 "C at 10 mmHg (lit.,' 96-99 "C at 12 mmHg; 68%); vmaX.…”

Photoisomerization of (Cyanomethylene)cyclopropane (C5H5N) to 1-Cyano-2-methylenecyclopropane in an Argon Matrix

“…The sample of (cyanomethylene)cyclopropane ( 5 ) used in this work was prepared by the Wittig reaction of 1-ethoxycyclopropanol and (cyanomethyl)triphenyl-phosphonium chloride, as described previously. , The synthesis of 1-cyano-2-methylenecyclopropane ( 7 ) followed the synthetic methodology that was first developed for the synthesis of hypoglycin A, a natural product found in unripe fruit from the Ackee tree . Carbon et al synthesized ethyl methylenecyclopropanecarboxylate by adding ethyl diazoacetate to 2-bromopropene in the presence of a copper–bronze catalyst followed by a sodium hydride-induced elimination (Scheme a). , Black and Landor utilized a zinc–copper-catalyzed reaction to generate the methylenecyclopropane moiety in a much higher yield (Scheme b) . More recently, Lai and Liu improved the yield of the ethyl diazoacetate route by utilizing a rhodium acetate catalyst (Scheme c) .…”

“… 43 , 44 Black and Landor utilized a zinc–copper-catalyzed reaction to generate the methylenecyclopropane moiety in a much higher yield ( Scheme 2 b). 45 More recently, Lai and Liu improved the yield of the ethyl diazoacetate route by utilizing a rhodium acetate catalyst ( Scheme 2 c). 46 Our synthesis of 7 closely follows the established route of Lai and Liu.…”