Pteridines.  XXVIII.  New, general, and unequivocal pterin synthesis

Taylor, Edward C.; Perlman, Katherine L.; Sword, I. P.; Sequin-Frey, Margareta; Jacobi, Peter A.

doi:10.1021/ja00800a042

Cited by 43 publications

(16 citation statements)

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“…Pyrazine and its derivatives ( 81 ) have potent application in cancer experimental drugs [83a] and it also shows antibacterial, antitumor and antibiotic activities [83b,c] . In 2018, Balaraman and co‐workers [44] demonstrated the first pyrazine ( 81 ) synthesis directly from β ‐amino alcohol via acceptorless dehydrogenation ( 31 ) using well defined dimeric cobalt complex ( Co‐2 ) (Scheme 35).…”

Section: Synthesis Of Aromatic Heterocycles Via Catalytic De(hydrogenation)mentioning

confidence: 99%

Recent Progress in the Synthesis of Heterocycles through Base Metal‐Catalyzed Acceptorless Dehydrogenative and Borrowing Hydrogen Approach

et al. 2021

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Development in the area of acceptorless dehydrogenation (AD) and borrowing hydrogen (BH) catalysis emerge as one of the potential tools for various CÀ C and C-heteroatom bond forming reactions. Alcohols, which are important lignocellulosic biomass products, act as pivotal electrophilic coupling partners in such processes and interestingly only H 2 or H 2 O is eliminated as a byproduct. Initially, the area was developed by the use of noble metal catalysts. Recently, base metals such as Mn, Fe, Co, and Ni proved to be environmentally benign and inexpensive alter-natives for the noble metals in the application of AD and BH methods. This transition metal catalyzed AD and BH approaches also allow access toward a plethora of structurally important heterocyclic molecules via environmentally benign and atom economical strategy. Herein, we summarize the current and rising expansion of base metal catalyzed heterocycles synthesis through acceptorless dehydrogenation and borrowing hydrogenation strategy.

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Section: Synthesis Of Aromatic Heterocycles Via Catalytic De(hydrogenation)mentioning

confidence: 99%

Recent Progress in the Synthesis of Heterocycles through Base Metal‐Catalyzed Acceptorless Dehydrogenative and Borrowing Hydrogen Approach

et al. 2021

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“…2 was also converted into 6-bromomethylpterin hydrobromide (25 ) by HBr treatment according to literamre (32). Its reactivity was proven by treatment with sodium or triethylammonium salts of various acids to give the corresponding 6-acyloxy-methylpterins 33, 34, and 36-38. hnally the amino group in 6-hydroxymethyl-pterin (24) was protected by reaction with N ,N-dimethylformamide dimethylacetal to give 2-(N , N -dimethylaminomethylene-imino) -6-hydnn .…”

Section: Synthesismentioning

confidence: 99%

“…Some efforts have been undertaken to substitute the h ydrophilic side-chain of tetrahydrobiopterin against more lipophilic 6-alkoxymethyl groups (20,21,22) to overcome the limitations of ~Bip. So far the synthesis of 6 -alkoxymethyl-2,4-diaminopteridines and -pterins (22,23 ) have been based on a Taylor reaction (24)(25)(26) builcling up the pteridine ring-systems from a pyrazine intermecliate. Condensation of aminomalononitrile and chloromethylglyoxalmonoxime lead in a regioselective reaction to 2-amino-S-chioromethyl-3-cyanopyrazine i-oxide, which can either clirectly or after deoxygenation been converted into the corresponcling alkoxymethyl derivatives and subsequent reaction with guanidine to give the 6-alkoxymethyl-2,4-cliaminopteridines and 8-oxides, respectively.…”

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confidence: 99%

Pteridines CX

Traub

Pfleiderer

1999

Pteridines

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SummaryA series of new 6-substituted 2,4-diaminopteridines (3-23) and pterins (26-43) have been synthesized by nucleophilic displacement reactions at the side chain of 6-bromomethyl-2,4-diaminopteridine (2) and 6-bromomethylpterin (25) using various types of 0-, N-and S-nucleophiles. Acid and base hydrolyses allow easy conversion of the 2,4-diaminopteridines (3-5, 7, 9, 10, 12, 19-21 and 23) into the corresponding pterins (26-32, 39-42). Acylations take place at the amino as well as at the functional groups in the side chain (44-46). A versatile protection of the amino group in pterins is its transformation into the N ,N -dimethylaminomethylcnimino function by amide-acetals (47, 50) allowing subsequently selective acylations at the side chain (48, 49).

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“…For this reason, formation of acylpterins is typically done through oxidation of alkyl side-chains to carboxylates or alcohols 4,5. Taylor developed a method for forming isomerically-pure alkyl pterins, though it requires a multi-step construction of the ring 6. Methods exist for the formation of isomerically-enriched alkyl pterins through a traditional one step condensation, but formation of the undesirable isomer is still observed 5.…”

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Acyl radical insertion for the direct formation of new seven-substituted pterin analogs

Pruet

Robertus

Anslyn

2010

Tetrahedron Letters

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A variety of pterin molecules were synthesized via an under-utilized acyl radical insertion, using aldehydes and α-keto esters as the acyl source. These reactions gave complete regiospecificity for the 7-isomer, with reaction times ranging in minutes, often with instantaneous product precipitation. This approach led to the construction of new pterin analogs unaccessable via traditional FriedelCrafts acylation. The compounds were characterized by NMR spectroscopy and high-resolution mass spectroscopy.Pterins have been shown to be a noteworthy lead in the search for Ricin A chain inhibitors. 1 In this context, we have explored different routes to pterin libraries, particularly those which remove extraneous steps often needed to circumvent pterins' insolubility and poor reactivity. As with other diazoaromatic compounds, such as pyrazines, direct substitution by electrophiles is not a viable reaction for pterins, as a result of their being so π-electron deficient. 2,3 For this reason, formation of acylpterins is typically done through oxidation of alkyl side-chains to carboxylates or alcohols. 4,5 Taylor developed a method for forming isomerically-pure alkyl pterins, though it requires a multi-step construction of the ring. 6 Methods exist for the formation of isomerically-enriched alkyl pterins through a traditional one step condensation, but formation of the undesirable isomer is still observed. 5 Furthermore, due to the poor solubility of pterins, isolation of the desired isomer can be difficult, often requiring further modifications. 5,7 Direct acylation of heteroaromatic bases was first shown by Caronna, whereby an aldehyde is allowed to react with a peroxide in the presence of iron sulfate, generating an acyl radical which can insert onto the protonated heterocyclic species. 8 This reaction has been performed on a variety of simple heterocycles, and has also been shown to proceed with α-keto esters as the acyl source. 2,9,10 Substituent-directing effects have been studied, and it was found that groups which are electron withdrawing by resonance and inductive effects direct to the para position. 11 As related to pterins, these directing effects would regiospecifically provide the 7-isomer. This reaction has previously been utilized on molecules containing the general pteridine substructure, and it was indeed found that when both heteroaromatic positions are available, only the 7-isomer is formed, while placement of electron-donating substituents on the 7-position allowed access to the 6-isomer. 12-14 However, these pteridine analogs often had *Corresponding author. Tel.: 512-471-0068; fax: 512-471-7791; anslyn@austin.utexas.edu. Supplementary MaterialSupplementary data (general experimental procedure, NMR and MS data) can be found in the online version.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and rev...

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Pteridines. XXVIII. New, general, and unequivocal pterin synthesis

Cited by 43 publications

References 1 publication

Recent Progress in the Synthesis of Heterocycles through Base Metal‐Catalyzed Acceptorless Dehydrogenative and Borrowing Hydrogen Approach

Recent Progress in the Synthesis of Heterocycles through Base Metal‐Catalyzed Acceptorless Dehydrogenative and Borrowing Hydrogen Approach

Pteridines CX

Acyl radical insertion for the direct formation of new seven-substituted pterin analogs

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