Rearrangement of N<sub>α</sub>-Protected <scp>l</scp>-Asparagines with Iodosobenzene Diacetate. A Practical Route to β-Amino-<scp>l</scp>-alanine Derivatives

Zhang, Linhua; Kauffman, Goss S.; Pesti, Jaan A.; Yin, Jianhua

doi:10.1021/jo9702756

Cited by 102 publications

(72 citation statements)

References 23 publications

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“…In fact, an enantiopure bicyclic d-lactam 79 was used as precursor of an N-acyliminium ion for the highly diastereoselective addition of trimethylsilyl cyanide (80 enantiopure dimethoxyimidazolidinone 84, generated in five steps from a nonchiral imidazolone 83, underwent nucleophilic addition of isobutylcyanocuprate to an in situ generated acyliminium ion followed by introduction of a tosyl group and removal of the chiral auxiliary (MAC) to afford an N-tosyl methoxyimidazolidinone 85 that was submitted to diastereoselective Lewis acid mediated addition of cyanotrimethylsilane (86). Finally, four steps, including acidic hydrolysis of the cyanide group and imidazolidinone cleavage, rendered the enantiopure syn a,b-diamino ester 87 in good yield (Scheme 9.11) [66].…”

Section: Nucleophilic Synthetic Equivalents Of Co 2 Rmentioning

confidence: 99%

“…In many of these examples the Garners aldehyde obtained from L-serine is an essential synthetic intermediate [84]. Aside from using b-hydroxy amino acids, a common approach to L-2,3-diaminopropionic acid involves either a Curtius rearrangement of free L-aspartic acid or a Hofmann reaction of an L-asparagine derivative [85,86]. The main side-products in these reactions are imidazolidinones [87]; however, a clever use of the reagents can provide orthogonally protected L-2,3-diaminopropionic acid [88].…”

Section: From Readily Available A-amino Acidsmentioning

confidence: 99%

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Synthetic Approaches to α,β‐Diamino Acids

Viso

Pradilla

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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Section: Nucleophilic Synthetic Equivalents Of Co 2 Rmentioning

confidence: 99%

Section: From Readily Available A-amino Acidsmentioning

confidence: 99%

Synthetic Approaches to α,β‐Diamino Acids

Viso

Pradilla

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…The key intermediate 2,3-diaminopropionic acid (8) was prepared from Boc-Ser-OMe under Mitsunobu conditions 19) or from Boc-Asn-OMe with iodosobenzene diacetate. 20) Using N-ethyl NЈ-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/1-hydroxy- benzotriazol (HOBt) as the coupling reagent, a fully protected peptide (9a) was obtained from compound 7 and 8 after easy work-up. The original amino acid compound 6 was obtained by saponification of the ester in 9a, followed by treatment with 4 N hydrogen chloride in ethyl acetate (4 N HCl in EtOAc).…”

Section: Design and Synthesis Of Carboxylate Inhibitors For Matrix Mementioning

confidence: 99%

“…In order to avoid dehydration, N 2 ,O-diprotected 2(S),3(S)-diaminobutanol (20) was prepared from Boc-Thr-OH according to the procedure described by Nakamura et al 21) After condensation of 20 and tripeptide (7a)…”

Section: Design and Synthesis Of Carboxylate Inhibitors For Matrix Mementioning

confidence: 99%

Design and Synthesis of Carboxylate Inhibitors for Matrix Metalloproteinases.

Fujisawa

Katakura

Odake

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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Matrix metalloproteinases (MMPs) are zinc endometallopeptidases that are involved in the degradation and remodeling of connective tissues. This family of enzymes shows proteolytic activity towards virtually all of the constituents of the extracellular matrix. The members of this family, currently numbering 20, can be classified into four groups, which are the collagenases that cleave triple-helical interstitial collagen; the gelatinases that cleave denatured collagen, elastin, and type IV and V collagen; the stromelysins that mainly cleave proteoglycans; and the membrane-type MMPs that have a C-terminal transmembrane domain for anchoring to the cell membrane. The MMPs are involved in crucial physiological and physiopathological events, such as wound healing, nerve growth, angiogenesis, and pregnancy. In these physiological processes, MMP activity is tightly regulated. [1][2][3][4][5] However, excessive MMP synthesis and release can lead to connective tissue degradation and destruction, which occurs in tumor invasion, metastasis, 6) corneal ulceration, 7) arthritis disease, 8a) periodontal disease, 9) and multiple sclerosis. 10) For example, increased levels of fibroblast collagenase (MMP-1) and stromelysin-1 (MMP-3) have been observed in the cartilage and synovium of patients with rheumatoid arthritis and osteoarthritis, and are correlated with the severity of the disease. 8b) Therefore, MMPs inhibitors may have a potent therapeutic effect on various proteolytic diseases.Many MMP inhibitors have been synthesized and developed. Several compounds are currently undergoing advanced clinical trials, such as batimastat (1), 11) marimastat (2), 12) trocade (3), 13) and AG3340 (4) 14) (Fig. 1). These inhibitors mimic the sequence of the substrate-cleavage site of MMPs and have hydroxamate as a zinc-chelating group (ZCG). This kind of design has been widely applied for other MMPs inhibitors.Previously, we also developed a series of peptidyl hydroxamates as MMP-1 inhibitors (Fig. 2), 15) our compounds mimicked the P 4 -P 1 substrate rather than the P 1 -P 1 Ј or P 1 -P 2 Ј sites in the above-mentioned MMP inhibitors (1)-(4). Inhibitors that mimic the P n Ј site have been studied extensively but little is known about P n site-mimicking inhibitors like our compounds because of their only modest inhibitory potency (IC 50 values in the order of 10 Ϫ6 M for MMP-1). However, we thought that this type of inhibitor could show further improvement of its inhibitory activity, since hydroxamate 15) and phosphorous 16) have been examined as ZCGs. Design Beside hydroxamate and phosphorous, the ZCGs utilized most frequently are thiol or carboxylate. The free thiols are unstable to oxidation in air at neutral pH during preparation and storage. 17) To avoid the disadvantage, we selected a carboxylate, which was expected to be relatively stable and to show good pharmacokinetics, as the ZCG. Although the carboxylate is a weaker ZCG than the others for MMP-1, 5) we designed the 2,3-diaminopropionic acid derivative (6) to compensate for thi...

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“…5 Following the same strategy, the first step in our modified route to the synthesis of the enantiomerically pure alkyl chain of anatoxin-a(s) was Fmoc protection of L-asparagine in 83% yield (Scheme 1). 20 Fmoc-N-L-asparagine (2) was then treated with [bis(trifluoroacetoxy)iodo]benzene, 21 The production of molecules in racemic form has been used in several areas of interest. This strategy can lead to gains in overall efficiency.…”

mentioning

confidence: 99%

Synthesis of Cyclic Guanidine Intermediates of Anatoxin-a(s) in Both Racemic and Enantiomerically Pure Forms

Moura¹,

Pinto²

2010

Synlett

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The alkyl chain of anatoxin-a(s) (cyclic guanidines), which can be used as an intermediate in the total synthesis of anatoxin-a(s), was synthesized in both racemic and enantiomerically pure forms. These enantiomerically pure cyclic compounds can be used as chiral inductors in some reactions. The two racemic routes disclosed herein have the advantages of high overall yield and mild reaction conditions. Both routes proceed through an intermediate 2,3-diaminoacid -an important synthetic scaffold -with good yields. Furthermore, the N,N-dimethyl-2(tosylimino)imidazolidine-4-carboxamide might be obtained from 2-(tosylimino)imidazolidine-4-carboxylic acid followed by selective reduction of the carbonyl functionality. All synthesized compounds were analyzed by mass spectrometry and 1 H NMR and 13 C NMR spectroscopy.

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Rearrangement of N_α-Protected l-Asparagines with Iodosobenzene Diacetate. A Practical Route to β-Amino-l-alanine Derivatives

Cited by 102 publications

References 23 publications

Synthetic Approaches to α,β‐Diamino Acids

Synthetic Approaches to α,β‐Diamino Acids

Design and Synthesis of Carboxylate Inhibitors for Matrix Metalloproteinases.

Synthesis of Cyclic Guanidine Intermediates of Anatoxin-a(s) in Both Racemic and Enantiomerically Pure Forms

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Rearrangement of Nα-Protected l-Asparagines with Iodosobenzene Diacetate. A Practical Route to β-Amino-l-alanine Derivatives

Cited by 102 publications

References 23 publications

Synthetic Approaches to α,β‐Diamino Acids

Synthetic Approaches to α,β‐Diamino Acids

Design and Synthesis of Carboxylate Inhibitors for Matrix Metalloproteinases.

Synthesis of Cyclic Guanidine Intermediates of Anatoxin-a(s) in Both Racemic and Enantiomerically Pure Forms

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Product

Resources

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Rearrangement of N_α-Protected l-Asparagines with Iodosobenzene Diacetate. A Practical Route to β-Amino-l-alanine Derivatives