Preparation and Properties of Nalpha-Di-tert-Butoxycarbonyl Amino Acids. Applicability in the Synthesis of Leu-Enkephalin.

Gunnarsson, Kerstin; Ragnarsson, Ulf; Halme, Marjo H.; Loponen, Jyrki; Euranto, Erkki K.; Pettersson, Tore

doi:10.3891/acta.chem.scand.44-0944

Cited by 35 publications

(15 citation statements)

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“…Note: N,N 0 -di-Boc-amino acids are also prepared starting from Boc-amino acid allyl esters [125]. Note: The above procedure gives good yields particularly for Gly.…”

Section: Photocleavable Protectionsmentioning

confidence: 99%

“…In this regard, benzyl, 1.2.2.5.4 N a ,N a -bis-Protected Amino Acids Double protection of the nitrogen of the a-amino group is occasionally required to avoid side-reactions arising from the acidic -NH proton of the urethane linkage of N a -protected amino acids/peptides. The N a ,N a -bis-Boc protection is introduced by the treatment of benzyl esters of Bocamino acids with (Boc) 2 O in the presence of 4-(dimethylamino)pyridine (DMAP) in CH 3 CN, followed by catalytic hydrogenation [124,125]. The product is purified from the possible N-mono-Boc-contaminants by recrystallization in petroleum ether.…”

Section: Introduction Of Urethanes Via Transprotectionmentioning

confidence: 99%

“…The product is purified from the possible N-mono-Boc-contaminants by recrystallization in petroleum ether. N a -Z,N a -Boc-amino acids are prepared by treatment of 9-fluorenylmethyl esters of Z-amino acids with (Boc) 2 O in the presence of DMAP followed by cleavage of the ester with piperidine [125]. The N a ,N a -bis protected derivatives can be synthetically valuable compounds.…”

Section: Introduction Of Urethanes Via Transprotectionmentioning

confidence: 99%

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Protection Reactions

Sureshbabu¹,

Narendra²

2011

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…Note: N,N 0 -di-Boc-amino acids are also prepared starting from Boc-amino acid allyl esters [125]. Note: The above procedure gives good yields particularly for Gly.…”

Section: Photocleavable Protectionsmentioning

confidence: 99%

Section: Introduction Of Urethanes Via Transprotectionmentioning

confidence: 99%

Section: Introduction Of Urethanes Via Transprotectionmentioning

confidence: 99%

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Protection Reactions

Sureshbabu¹,

Narendra²

2011

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…The remaining C3-hydroxy group of 6 then was conjugated with the less sterically cumbersome glycine A, 27) followed by construction of the pyrrole ring on-site via reaction with 1,3-bis(dimethylamino) allylium tetrafluoroborate B.…”

Section: )mentioning

confidence: 99%

“…25,26) Pentaol 7, which was constructed from 2,5-dimethylbenzene-1,4-diol (8), was regioselectively protected as the two boronate esters to yield 6. The remaining C3-hydroxy group of 6 then was conjugated with the less sterically cumbersome glycine A, 27) followed by construction of the pyrrole ring on-site via reaction with 1,3-bis(dimethylamino) allylium tetrafluoroborate B.…”

Section: )mentioning

confidence: 99%

Chemical Conversion of Ryanodol to Ryanodine

Masuda

Nagatomo

Inoue

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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Ryanodine (1) is a plant-derived natural product with powerful pharmacological and insecticidal action, and is a potent modulator of intracellular calcium release channels. Compound 1 possesses a 1H-pyrrole-2-carboxylate ester at the C3-position of heptahydroxylated terpenoid ryanodol (2). Whereas 2 was readily obtained from 1 by basic hydrolysis, 1 has never been synthesized from 2, due to the extreme difficulty in selectively introducing the bulky pyrrole moiety at the severely hindered C3-hydroxyl group of heptaol 2. Here we report chemical conversion of 2 to 1 for the first time. The derivatization was realized through the use of a new protective group strategy and the application of on-site construction of the pyrrole-2-carboxylate ester from the glycine ester and 1,3-bis(dimethylamino)allylium tetrafluoroborate.Key words acylation; protecting group; regioselectivity; ryanodine; terpenoid Ryanodine (1, Chart 1) has been isolated from the wood of Ryania speciosa VAHL and shown to possess potent insecticidal and pharmacological actions.1) Compound 1 binds specifically to a high-conductance intracellular calcium channel known as the ryanodine receptor (RyR), altering its conductance.2,3) Since the RyR plays an important role in many biological processes and malfunctions in its action have been linked to skeletal and cardiac diseases, 4-7) 1 has been used as a biological probe for investigations of RyR function, and is regarded as a strong candidate in the development of therapeutic agents for various diseases. [8][9][10] In 1968, the structure of ryanodine (1) was determined to be the ester between 1H-pyrrole-2-carboxylic acid (3) and the C3-hydroxyl group of ryanodol (2). [11][12][13][14] Compound 2 is a diterpenoid containing the exceedingly complex five fused rings (ABCDE-rings) with eleven contiguous stereocenters. Interestingly, the affinity of 2 toward RyRs of vertebrate skeletal muscle is 1700 times weaker than that of 1 (K D =7 nM), [15][16][17] demonstrating that the pyrrole group is a primary determinant for strong interactions of 1. Because of its important biological activities and intriguing structural features, many studies attempting the chemical construction of 1 has been carried out, which resulted in the total syntheses of ryanodol (2) by the Deslongchamps group in 1979 18,19) and by our laboratory in 2014. [20][21][22] In 1951, before the complete structure of 1 was known, Wiesner and colleagues found that basic hydrolysis of ryanodine (1) generated 2 and 3.11) However, the reverse reaction has not been realized even to date. The difficulty of the transformation arises from the need to control the regioselectivity of the four tertiary (C2, 4, 6, 12), two secondary (C3, 10) and one acetalic (C15) alcohols within heptaol 2 and to accommodate the bulky pyrrole moiety at the hindered C3-hydroxyl group. The computer-generated 23) structure of 2 revealed that its axially oriented C3-OH was shielded by the proximal C14-hydrogen atom and by the C19-, 20-methyl groups (Fig. 1). In fact, direct esteri...

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Crystal structures of peptides and modified peptides

Marraud

Aubry

1996

Biopolymers

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The X‐ray diffraction experiments on peptides and related molecules which have been carried out in Western Europe, except Italy, in the last eight years are reviewed. The crystal structures of some bioactive peptides such as Leu‐enkephalin (a neurotransmitter), cyclosporin A (an immunomodulator in both the free and protein‐bound state), balhimycin (an antibiotic) and octreotide (a somatostatin analogue) are briefly presented. Crystallized N‐ and C‐protected model peptides have given an insight into the folding tendency and folding modes depending on the peptide sequences. The crystal structures of various pseudopeptide molecules reveal how the three‐dimensional structure of peptide analogues can be modulated by substituting non‐peptide groups for the peptide bond. A few examples of structural mimetics of the β‐ and γ‐turns, and of templates for α‐helix induction are also presented. © 1996 John Wiley & Sons, Inc.

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Preparation and Properties of Nalpha-Di-tert-Butoxycarbonyl Amino Acids. Applicability in the Synthesis of Leu-Enkephalin.

Cited by 35 publications

References 0 publications

Protection Reactions

Protection Reactions

Chemical Conversion of Ryanodol to Ryanodine

Crystal structures of peptides and modified peptides

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