A New Synthesis of Ciliapterin and Dictyopterin. Ene Reactions of (Alkenylamino)‐nitroso‐pyrimidines

Zhang, Fang-Li; Vasella, Andrea

doi:10.1002/hlca.200890255

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…[46] Dictyopterin is thought to be involved in the transition from the unicellular to the multicellulars tage of the social amoebae; tetrahydrodictyopterin productionw as linked to the early developmental stages of D. discoideum. [47] The synthesis of dictyopterin( 134)b yZ hang et al [48] (Scheme13) began with conversion of pentenol 128 to pentenamine 129 that was achieved by aM itsunobu reactionw ith phthalimide as nucleophile, followed by treatment with hydrazine. Amine 129 underwent nucleophilic aromatic substitution Scheme12.…”

Section: Dictyopterinmentioning

confidence: 99%

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Natural Products from Social Amoebae

Barnett

Stallforth

2017

Chemistry A European J

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Natural products are invaluable sources of structural diversity and complexity ideally suited for the development of therapeutic agents. The search for novel bioactive molecules has prompted scientists to explore various ecological niches. Microorganisms have been shown to constitute such an important source. Despite their biosynthetic potential, social amoebae, that is, microorganisms with both a uni- and multicellular lifestyle, are underexplored regarding their secreted secondary metabolome. In this review, we present the structural diversity of amoebal natural products and discuss their biological functions as well as their total syntheses.

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Section: Dictyopterinmentioning

confidence: 99%

“…The synthesis of dictyopterin ( 134 ) by Zhang et al . (Scheme ) began with conversion of pentenol 128 to pentenamine 129 that was achieved by a Mitsunobu reaction with phthalimide as nucleophile, followed by treatment with hydrazine.…”

Section: Other Compoundsmentioning

confidence: 99%

Natural Products from Social Amoebae

Barnett

Stallforth

2017

Chemistry A European J

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“…Acylation of 5 at the C(4)ÀNHMe group differs from the one of analogous nitrosopyrimidines possessing a C(4)ÀNH 2 group that leads to amides that are sufficiently stable to be isolated in spite of their activation by conjugation with the NO group. This difference is explained by pointing out that the N-acyl-N-methyl amino group can no longer form a favourable intramolecular H-bond from the acylamino NH to the NO group [7] [4]. To substantiate the hypothesis that the C(4)ÀNHMe group is reversibly acylated, and that the amide can be trapped by an irreversible follow-up reaction, we treated 5 with hexadienoyl chloride (Scheme 3).…”

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confidence: 96%

Acylation of a 6‐(Methylamino)‐5‐nitrosopyrimidine and 1,3‐Dipolar Cycloaddition of an 8‐Methylisoxanthopterin N(5)‐Oxide. Synthesis of C(6),N(8)‐Disubstituted Isoxanthopterins

Steinlin

Vasella

2009

Helvetica Chimica Acta

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Acylation of 2-amino-4-(benzyloxy)-6-(methylamino)-5-nitrosopyrimidine (5) with acetic anhydride or chloroacetic anhydride in the presence of 4-(dimethylamino)pyridine (DMAP) led to the C(2)-acylamino derivatives 6 and 7, respectively. In the absence of a base, acetylation did not lead to a product, while chloroacetylation led to the 6-chloropteridine 11. Chloroacetylation in the presence of Hünigs base provided the pteridinone N(5)-oxide 10, suggesting that acylation of 5 is readily reversible, and that the unfavourable equilibrium must be displaced by a follow-up reaction to trap the acylation product. Acylation of 5 with hexadienoyl chloride, followed by intramolecular Diels -Alder reaction, provided the pteridinone 12. A high yielding 1,3-dipolar cycloaddition of the acylnitrone 10 to electron-poor and electron-rich dipolarophiles, followed by spontaneous N,O-bond cleavage, gave the C(6)-substituted pteridinones 19a -19e that were deprotected to the pteridine-4,7(3H,8H)-diones 20a -20e. Substitution of the 6-chloropterin 11 provided the 6-morpholinopteridine 25. Sonogashira coupling yielded the fluorescent [(pteridin-6-yl)ethynyl]-glucopyranoside 26, 6-ethynylpteridine 28, and 6,6'-(ethynediyl)-bispteridine 29. The alkyne 28 reacted with Me 3 SiCl and LiBr in MeCN to produce the bromoalkene 31.Introduction. -We described new routes to 6-substituted pteridines based on intramolecular Diels -Alder cycloadditions, ene-reactions, and condensations of N(6)-acylated or N(6)-alkylated 6-amino-5-nitrosopyrimidines [1 -4]. We also showed that the pteridinone N(5)-oxides, resulting from the condensation of 6-amino-5-nitrosopyrimidines with chloroacetic acid anhydride ((ClCH 2 CO) 2 O) react as acylnitrones. The course of their [3 þ 2] cycloaddition to acceptor-substituted dipolarophiles is illustrated in Scheme 1 by the addition of 1 to methyl acrylate. This reaction provides 2, resulting from a spontaneous eliminative cleavage of the N,O bond of the initially formed isoxazolidine, and thus constitutes a new, high-yielding access to isoxanthopterins 2 possessing a functionalised side chain at C(6) [5]. The poor solubility of these isoxanthopterins was assumed to result from a favourable intermolecular H-bonding of the DADA motif involving HN(2'), N(1'), HN(8') and O¼C(7') of the products of type 2. This hypothesis prompts to investigate the formation and 1,3-dipolar cycloaddition of N(8)-alkyl derivatives of 1. The simplest ones, N(8)-methylpteridinone N(5)-oxides, should be obtained by an intramolecular condensation of 6-[(chloroacetyl)(methyl)-amino]-5-nitrosopyrimidines. We were thus interested in the cycloaddition of N(8)-alkylated pteridinone N(5)-oxides and the solubility of the resulting products, in the formation of the pteridinone N-oxides by condensation of 6-[(alkyl)(chloroacetyl)-amino]-5-nitrosopyrimidines, and in the N-acylation leading to these amides. As we had

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