Practical Asymmetric Approach to Pyrrolidinones:  Efficient Synthesis of (+)-Preussin and (−)-AHPPA

Kanazawa, Alice; Gillet, Sandra; Delair, Philippe; Greene, Andrew E.

doi:10.1021/jo9801162

Cited by 62 publications

(9 citation statements)

References 20 publications

(19 reference statements)

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“…Two other β-hydroxy-γ-amino acids, (−)-AHPPA 40 and (−)-detoxinine, 41 have also been prepared in our laboratory by using these key transformations. The chiral pyrrolidinones were obviously also potential precursors of pyrrolidine natural products, such as (+)-preussin 40 and (−)-anisomycin. 42 Our short preparation of the former, summarized in Scheme 12, demonstrated this feasibility.…”

Section: ■ Five-and Four-membered Carbocyclesmentioning

confidence: 99%

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Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

et al. 2016

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11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded γ-butyrolactam, γ-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both. The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of α,α-dichlorocyclobutanones from olefins provided the starting point for decades' worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaianolides, azulenes) could thus be prepared by using dichloroketene-olefin cycloaddition, followed by regioselective one-carbon ring expansion with diazomethane. Importantly, it was also found that natural γ-butyrolactones (e.g., β-oxygenated γ-butyrolactones, lactone fatty acids) could be secured through regioselective Baeyer-Villiger oxidation of cycloadducts with m-CPBA and that naturally occurring γ-butyrolactam derivatives (e.g., amino acids, pyrrolidines, pyrrolizidines, indolizidines) could be efficiently obtained by regioselective Beckmann ring expansion of the adducts with O-(mesitylenesulfonyl)hydroxylamine (Tamura's reagent). These 5-membered carbocycles, γ-butyrolactones, and γ-butyrolactam derivatives were generally secured in enantiopure form through the use of either intrinsically chiral olefins or olefins bearing Stericol, a highly effective chiral auxiliary developed specifically for this "three-atom olefin annelation" approach. In addition, considerable useful chemistry has been developed in the context of this synthesis program. This includes new methods for olefin vicinal dicarboxylation, β-methylene-γ-butyrolactonization, γ-butyrolactone and δ-valerolactone α-methylenations, transesterification, angelic ester synthesis, chiral enol and ynol ether preparations, dichloroacetylene synthesis, and trans, trans hydroxy triad introduction. This versatile dichlorocyclobutanone-centered approach to natural product synthesis, together with the attendant new methods that have been developed, forms the basis of this Account, which is presented as an evolutionary tale. It is hoped that the Account will stimulate other research groups to seek to exploit the rich chemistry of dichlorocyclobutanones for possible solutions to problems in organic synthesis.

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Section: ■ Five-and Four-membered Carbocyclesmentioning

confidence: 99%

“…Recrystallization of pyrrolidinone 92 , followed by treatment with acid, provided enantiopure (−)-statine. Two other β-hydroxy-γ-amino acids, (−)-AHPPA and (−)-detoxinine, have also been prepared in our laboratory by using these key transformations.…”

Section: γ-Butyrolactam Derivativesmentioning

confidence: 99%

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

et al. 2016

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“…Other methods have also been used to prepare statine and related analogs, such as chromatographic resolution of a-methoxyphenylacetates [307], the cycloaddition of chiral enol ethers with dichloroketene coupled with the Beckmann ring expansion [308,309], and the addition of cyanide to 4-alkoxy-trichloro-but-3-en-2-ones which occurs with poor diastereoselectivity [310]. catalyzed by a stoichiometric amount of the Cinchona alkaloid proceeded smoothly to yield a mixture of the ester (424) and the dioxanone (425).…”

Section: B-hydroxy-g-substituted G-amino Acidsmentioning

confidence: 99%

Synthesis of γ‐Aminobutyric Acid Analogs

Hanrahan

Johnston

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…A large number of these rely on derivatization of readily available chiral pool materials: elaboration of l -phenylalanine facilitated the second synthesis of (+)-preussin that was reported, and this material (or derivatives thereof) has proven to be the most popular starting material by far in subsequent syntheses, − although (in chronological order) d -phenylalanine, d -arabinose, l -aspartic acid, l -pyroglutaminol, , l -serine, , and ( S )-malic acid , (or derivatives thereof) have also been employed as the sources of chirality. Other de novo asymmetric syntheses have been developed, − along with one formal synthesis of (+)-preussin − and two syntheses of (−)-preussin. , Moreover, the synthesis of all eight possible stereoisomers (using an enantiopure phenylalanine derivative as the starting material, proceeding via two nonselective reactions and chromatographic separation) has been reported, − as well as one synthesis of (±)-preussin. , The truncated analogue (+)-preussin B, (2 S ,3 S ,5 R )- N (1)-methyl-2-benzyl-5-(1′-heptyl)pyrrolidin-3-ol (Figure ), was isolated [along with (+)-preussin] in 2014 from Simplicillium lanosoniveum TAMA 173 and was shown to exhibit weak antifungal activity . The first and, to date, the only synthesis of (+)-preussin B to be reported is that of Huang et al, who employed ( S )-malic acid as their starting material .…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (−)-Preussin B, and 3-Deoxy-(+)-preussin B

et al. 2016

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Efficient de novo asymmetric syntheses of (+)-preussin B, the C(2)-epimer of (-)-preussin B, and 3-deoxy-(+)-preussin B have been developed, using the diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 4-phenylbut-2-enoate and diastereoselective reductive cyclizations of γ-amino ketones as the key steps to set the stereochemistry. Conjugate addition followed by enolate protonation generated the corresponding β-amino ester. Homologation using the ester functionality as a synthetic handle gave the corresponding γ-amino ketone. Hydrogenolytic N-debenzylation was accompanied by diastereoselective reductive cyclization in situ; reductive N-methylation then gave 3-deoxy-(+)-preussin B as the major diastereoisomeric product. Meanwhile, the same conjugate addition but followed by enolate oxidation with (+)-camphorsulfonyloxaziridine gave the corresponding anti-α-hydroxy-β-amino ester. α-Epimerization by oxidation and diastereoselective reduction then gave access to the corresponding syn-α-hydroxy-β-amino ester. Homologation of both of these diastereoisomeric α-hydroxy-β-amino esters gave the corresponding β-hydroxy-γ-amino ketones. N-Debenzylation and concomitant diastereoselective reductive cyclization, followed by reductive N-methylation, provided the C(2)-epimer of (-)-preussin B and (+)-preussin B as the major diastereoisomeric products, respectively. The overall yields (from phenylacetaldehyde) were 19% for 3-deoxy-(+)-preussin B over seven steps, 8% for the C(2)-epimer of (-)-preussin B over nine steps, and 7% for (+)-preussin B over eleven steps.

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Practical Asymmetric Approach to Pyrrolidinones: Efficient Synthesis of (+)-Preussin and (−)-AHPPA

Cited by 62 publications

References 20 publications

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

Synthesis of γ‐Aminobutyric Acid Analogs

Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (−)-Preussin B, and 3-Deoxy-(+)-preussin B

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