Studies on the Synthesis of Insulin Peptides

Holland, Gerald F.; Cohen, Louis A.

doi:10.1021/ja01547a075

Cited by 51 publications

(16 citation statements)

References 6 publications

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“…Parham and DeLaitsch studied and compared the pyranylation of hydroxyl and thiol groups, observing higher reactivity for pyranylation of hydroxyl groups and less stability for the resulting tetrahydropyran acetal than for thioacetals . In 1958, Holland and Cohen addressed the introduction of DHP into Cys for the protection of the thiol group for the synthesis of insulin peptides in solution …”

Section: Thp Protection Of the Thiol Group (Cysteine)mentioning

confidence: 99%

“…In 1958, Holland and Cohen reported that the use of one equivalent of DHP in acidic medium resulted in blocking the carboxyl group in preference to the SH group. They reported that DHP, used in excess, reacted with N‐protected Cys to protect both SH and COOH functional groups, and the resulting compound was resistant to mild alkaline saponification . Additionally, Pappo and Bernady exploited the protection of the carboxyl function of prostaglandins with Thp.…”

Section: Thp Protection Of the Carboxyl Groupmentioning

confidence: 99%

“…[14,26] In 1958, Holland and Cohen addressed the introduction of DHP into Cys for the protection of the thiol group for the synthesis of insulin peptides in solution. [27] Althought hiol groups are protected most widely as thioethers, especially Trt-, Dpm-, and benzyl-like groups, developed in the labs of Yajima and Nishiuchi, S,O-acetal groups, such as Bom for Boc chemistry [28] and more recently methoxybenzyloxymethyl( MBom) for Fmoc chemistry, [29] have also been used. However,t hese derivatives can result in av ery lowl evel of racemization, hinder Bom and MBom synthesis, and hamper the quality of the final product because formaldehyde is formed as as ide product during cleavage andi sa ccompanied by concomitant hydroxymethylation.…”

Section: Generalmentioning

confidence: 99%

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Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry

et al. 2017

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Tetrahydropyranyl (Thp) is recognized as a useful protecting group for alcohols in organic synthesis. It has several advantages, including low cost, ease of introduction, general stability to most non‐acidic reagents, it confers good solubility, and the ease with which it can be removed if the functional group it protects requires manipulation. However, little attention has been paid to Thp in peptide chemistry. Provided here is a concise analysis of the Thp protection of various amino acid functionalities (OH, SH, NH and COOH) and its application to peptide synthesis. Thp is a useful moiety for the side‐chain protection of serine, threonine and cysteine and is suitable for the Fmoc/tBu solid‐phase peptide synthesis strategy. The immobilized version of 3,4‐dihydro‐2H‐pyran, the so‐called Ellman resin, is also discussed as a useful solid support for anchoring the side chains of serine, threonine and tryptophan residues.

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Section: Thp Protection Of the Thiol Group (Cysteine)mentioning

confidence: 99%

Section: Thp Protection Of the Carboxyl Groupmentioning

confidence: 99%

Section: Generalmentioning

confidence: 99%

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Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry

et al. 2017

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“…Therefore, the selective protecting group elimination is possible, depending on the acidic conditions used. As a result of years of studies in the field, there are several Cys protecting groups available; some of them are labile in low acid concentration such as Mmt [8], Trt [9][10][11] or Thp [12,13]; others are more stable in low concentrations of trifluoroacetic acid (TFA) but cleavable using higher quantity of TFA -Diphenylmethyl (Dpm) [9,11,14], tBu [15,16] or MBom [17] and moreover, there are groups which are completely stable to TFA and removable using harsh conditions such as HF, for example Bom [18], Meb or Mob [19][20][21] groups.…”

Section: Acid-labile Cys Protecting Groupsmentioning

confidence: 99%

Trends to Acid-Labile Cys Protecting Groups: Thp as an Efficient and Non-Aromatic Cys Protecting Group for Fmoc Chemistry

Ramos-Tomillero¹,

Rodríguez²,

Alberício³

2015

Peptides 2015, Proceedings of the 24th American Peptide Symposium

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“…Both have the advantage of being very lipophilic and, hence, improve the solubility of SNA intermediates in organic solvents. Other useful acid-labile protecting groups are monomethoxytrityl (MeOTr) [45] and tetrahydro-2H-pyran-2-yl (Thp) [46]. Thp has the disadvantage of a lower lipophilicity compared to the trityl groups.…”

mentioning

confidence: 99%

A Direct Synthesis of Nucleoside Analogs Homologated at the 3′‐ and 5′‐Positions

Schmidt

Eschgfäller

Benner

2003

Helvetica Chimica Acta

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A new route is presented to prepare analogs of nucleosides homologated at the 3'-and 5'-positions. This route, applicable to both the d-and l-enantiomeric forms, is suitable for the preparation of monomeric bishomonucleosides needed for the synthesis of oligonucleotide analogs. It begins with the known monobenzyl ether 3 of pent-2-yne-1,5-diol, which is reduced to alkenol 4. Sharpless asymmetric epoxidation of 4, followed by opening of the epoxide 5 with allylmagnesium bromide, gives a mixture of diols 6 and 7. Protection of the primary alcohol as a silyl ether followed by treatment with OsO 4 , NaIO 4 , and mild acid in MeOH, followed by reduction, yields (2R,3R) {{[(tert-butyl)diphenylsilyl]oxy}methyl}tetrahydro-2-(2-hydroxyethyl)-5-methoxyfuran ( methyl 3-{{[(tert-butyl)diphenylsilyl]oxy}methyl}-2,3,5-trideoxy-a/b-d-erythro-hexafuranoside; 10) (Scheme 1). Protected nucleobases are added to this skeleton with the aid of trimethylsilyl triflate (Scheme 2). The o-toluoyl (2-MeC 6 H 4 CO) and p-anisoyl (4-MeOC 6 H 4 CO) groups were used to protect the exocyclic amino group of cytosine. The bis-homonucleoside analogs 11 and 14a are then converted to monothiol derivatives suitable for coupling (Schemes 3 and 4) to oligonucleotide analogs with bridging S-atoms. This synthesis replaces a much longer synthesis for analogous nucleoside analogs that begins with diacetoneglucose ( 1,2 : 5,6-di-Oisopropylideneglucose), with the stereogenic centers in the final products derived from the Sharpless asymmetric epoxidation. The new route is useful for large-scale synthesis of these building blocks for the synthesis of oligonucleotide analogs.

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Studies on the Synthesis of Insulin Peptides

Cited by 51 publications

References 6 publications

Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry

Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry

Trends to Acid-Labile Cys Protecting Groups: Thp as an Efficient and Non-Aromatic Cys Protecting Group for Fmoc Chemistry

A Direct Synthesis of Nucleoside Analogs Homologated at the 3′‐ and 5′‐Positions

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