Protection and Deprotection of Fused 2-Amino-4(3H)-pyrimidinones: Conversion of Pterins and 5-Deazapterins to 2,4-Diamino Derivatives

Taylor, Edward C.; Otiv, S. R.; Durucasu, İnci

doi:10.3987/com-93-6395

Cited by 14 publications

(9 citation statements)

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“…All compounds described herein gave NMR, matrixassisted laser desorption ionization (MALDI)-time of flight MS, and UV-visible spectra in accord with their structures, and each key compound gave a passing elemental analysis. Compounds 3 (15), 9 a-c (16,17), 10 a-c (16,17), 13 a-c (16,17), 14a (18), 14 b and c (Y.M., S. V. Kolotuchin, and S.C.Z., unpublished work), 15 (16,17), 3,3,3-triphenylpropylamine (19), 6-bromo-5-deazapterin (20), and Gn-Br dendrons a-c (16,17) were prepared by known methods. Size standards 16 a and b were prepared by using the same precursors as for 15 and by analogous methods.…”

Section: Methodsmentioning

confidence: 99%

Discrete and polymeric self-assembled dendrimers: Hydrogen bond-mediated assembly with high stability and high fidelity

Corbin

Lawless

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

170

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Hydrogen bond-mediated self-assembly is a powerful strategy for creating nanoscale structures. However, little is known about the fidelity of assembly processes that must occur when similar and potentially competing hydrogen-bonding motifs are present. Furthermore, there is a continuing need for new modules and strategies that can amplify the relatively weak strength of a hydrogen bond to give more stable assemblies. Herein we report quantitative complexation studies on a ureidodeazapterin-based module revealing an unprecedented stability for dimers of its self-complementary acceptoracceptor-donor-donor (AADD) array. Linking two such units together with a semirigid spacer that carries a first-, second-, or third-generation Fré chet-type dendron affords a ditopic structure programmed to self assemble. The specific structure that is formed depends both on the size of the dendron and the solvent, but all of the assemblies have exceptionally high stability. The largest discrete nanoscale assembly is a hexamer with a molecular mass of about 17.8 kDa. It is stabilized by 30 hydrogen bonds, including six AADD⅐DDAA contacts. The hexamer forms and is indefinitely stable in the presence of a hexamer containing six ADD⅐DAA hydrogen-bonding arrays. A t the most fundamental level, the readout of stored information in biochemical systems requires both a code and the machinery for expressing the code (1). Distinction at the molecular level is critical in such processes and in its simplest form involves a molecular recognition event. The code may be, for example, the primary sequence of a polypeptide, which through a series of recognition events folds into a specific secondary or tertiary structure, or it may be a linear array of recognition sites that are sequentially processed through a distinctive engagement at each site. However, a distinctive chemical process alone (e.g., DNA base pairing) is not sufficient. It must be coupled with a biological process (e.g., replication) to be considered authentic information retrieval.Inspired by nature's ability to create extraordinarily complex systems from comparatively simple information codes, and with an eye toward creating nanoscale devices (2), chemists have sought to develop small molecules capable of self-assembling into larger structures (3-10). Molecular recognition sites within these small molecules carry the code that guide the assembly. Thus, the information retrieval process is expressed through the formation of the self-assembled structure, which can further manifest itself through the bulk properties of the material formed (11,12). Despite the many successful examples that have appeared over the past decade, the power of this biomimetic self-assembly strategy has not been fully realized largely because of the limited number of recognition motifs available, and, in particular, their relatively low stability (4, 13). Moreover, nearly all self-assembling systems reported to date use a single type of distinction. Developing systems where bi-or polyinstructional codes guide ...

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Section: Methodsmentioning

confidence: 99%

Discrete and polymeric self-assembled dendrimers: Hydrogen bond-mediated assembly with high stability and high fidelity

Corbin

Lawless

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

170

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“…One limitation often encountered with the synthesis of structurally diverse pterins is the notorious insolubility in most solvents. This can be dealt with by preemptive modifications to the pteridine core which disrupt the hydrogen-bond assembly, such as benzylation of the lactam oxygen or conversion of the exocyclic amine to the pivalic amide [12,13]. The installation and subsequent removal of these groups naturally affects the overall yield and time necessary to generate new pterins.…”

Section: Introductionmentioning

confidence: 99%

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

Bockman

Pruet

2020

Beilstein J. Org. Chem.

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The synthetic utility of pterins is often hampered by the notorious insolubility of this heterocycle, slowing the development of medicinally relevant pteridine derivatives. Reactions which expedite the development of new pterins are thus of great importance. Through a dual role of diazabicycloundecene (DBU), 7-carboxymethylpterin is converted to the soluble DBU salt, with additional DBU promoting an ester-to-amide transformation. We have explored this reaction to assess its scope and identify structural features in the amines which significantly affect success, monitored the reaction kinetics using a pseudo-first order kinetics model, and further adapted the reaction conditions to allow for product formation in as little as 5 min, with yields often >80%.

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“…[18] It has also been applied to activate position 4 of pyrido [2,3-d]pyrimidines for nucleophilic displacement reactions. [19] However, this methodology has never been applied to pyrido [4,3-d]pyrimidines. Prior to introduction of the 1,2,4-triazole at position 4, the exocyclic amino group of compound 6b was protected as an acetyl group by reaction with acetic anhydride in pyridine (Scheme 5).…”

Section: Chemistrymentioning

confidence: 99%

“…Diazotization of 14 in 6  HCl with sodium nitrite, followed by decomposition of the diazonium salt with cuprous chloride (Sandmeyer reaction) gave access to the 7-chloro derivative 27 in a low yield (34 %). [6,19] Sufficient material could be isolated to conduct a Suzuki-type reaction with (3,4-dimethoxphenyl)boronic acid, leading to the formation of compound 28 (Scheme 8). However, the low yield of the Sandmeyer reaction prevents us from using this approach for parallel chemistry purposes, and studies are currently conducted in order to obtain easier access to 7-chloro-substituted pyrido [4,3-d]pyrimidine compounds and will be reported in due course.…”

Section: Chemistrymentioning

confidence: 99%

Development of Synthetic Strategies for the Construction of Pyrido[4,3‐d]pyrimidine Libraries – the Discovery of a New Class of PDE‐4 Inhibitors

Jang

Jonghe²,

Gao³

et al. 2006

Eur J Org Chem

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The synthesis of a pyrido[4,3‐d]pyrimidine library from 4,6‐diamino‐2‐bromonicotinamide and 4,6‐diaminonicotinamide is described. A systematic variation of the substituents at positions 2, 4, 5 and 7 of the pyrido[4,3‐d]pyrimidine scaffold was carried out, leading to a wide variety of structural analogues. This strategy led to the discovery of a new structural class of PDE‐4 inhibitors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Protection and Deprotection of Fused 2-Amino-4(3H)-pyrimidinones: Conversion of Pterins and 5-Deazapterins to 2,4-Diamino Derivatives

Cited by 14 publications

References 0 publications

Discrete and polymeric self-assembled dendrimers: Hydrogen bond-mediated assembly with high stability and high fidelity

Discrete and polymeric self-assembled dendrimers: Hydrogen bond-mediated assembly with high stability and high fidelity

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

Development of Synthetic Strategies for the Construction of Pyrido[4,3‐d]pyrimidine Libraries – the Discovery of a New Class of PDE‐4 Inhibitors

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