Studies of Novel and Highly Efficient Peptide Coupling Reagents
Online published: 2004-01-10
设计合成了一类新型的、分别基于HOBt、HOAt、HOOBt、HOPfp和HOSu的亚胺正离子型缩合剂。其中HOBt衍生的亚胺正离子型缩合剂,无论是在反应活性还是产物光学纯度方面都大大优于脲正离子型缩合剂。这类缩合剂不仅可以用于酰胺和酯的合成,而且可以用于固、液相法合成小肽及生物活性肽,例如Leu 脑啡肽的合成。对这类缩合剂参与酰胺键形成反应的机理,也进行了研究。在卤代脲正离子型缩合剂基础上,设计并合成了α 卤代吡啶正离子型缩合剂BEP、FEP、BEPH、FEPH、α 卤代噻唑正离子型缩合剂BEMT和α 卤代苯并咪唑正离子型缩合剂CMBI。
李鹏 , 徐杰诚 . 新型高效多肽缩合剂的研究(英文)[J]. 中国科学院大学学报, 2004 , 21(1) : 125 -134 . DOI: 10.7523/j.issn.2095-6134.2004.1.020
A number of novel and highly efficient immonium-，p yridinium-，thiawlium-，and ben-zimidawlium-type peptide coupling reagents，such asBOMI，BDMP，BPMP，BEP，FEP，BEPH，FEPH，BEMT，and CMB I were designed and synthesized. The high efficiency of these onium salts has been evaluated and proved by model reaction tests and the successful synthesis of various oligopeptides and biologically active peptides both in solution and in the solid phase，for example Leu-enkep halin，the pentapeptide moiety of Dolastatin 15 and the immunosuppressive undecapep-tide Cyclosporin O. Based upon extensive studies of the structure-activity relationship of these coupling reagents，a preliminary guideline for the molecular design of onium-type coupling reagents was developed. These novel reagents have proved to be very useful in the synthesis of structurally challeneine nentides and nentidomimetics.
Key words： coupling reagent; molecular design; peptide synthesis; racemization; reactivity
[1] Albericio F，Chinchilla R，Dodsworth D J，Najera C. New trends in peptide coupling reagents. Organic Preparation and Procedures In-ternational,2001，33 (2-3):205-303
[2] Humphrey J M，Chamberlin A R. Chemical synthesis of natural product peptides:coupling methods for the incorporation of noncodedamino acids into peptides. Chemical Reviews,1997，97(G):2243-22GG
[3] Nicolaou K C，Vourloumis D，Winssinger N，Baran P S. The art and science of total synthesis at the dawn of the twentyfirst century.AnRewandte Chemie International Edition,2000，39(1):44-122
[4] Li P，Xu J C.(1 H-Benwtriawl-1-yloxy)-N,N’-dimethylmethaniminium hexachloroantimonate (BOMI)，a novel coupling reagent for solu-tion and solid-phase peptide synthesis. Journal of Peptide Research,2000，55(2):110-119
[5] Li P，Xu J C. BOMI a novel peptide coupling reagent. Tetrahedron Letters,1999，40 (18):3605-3608
[6] Li P，Xu J.C. 5-(1 H-Benzotriazol-1-yloxy)-3，4-dihydro-l-methyl 2 H-pyrrolium hexachloroantimonate (BDMP}:。highly efficientimmonium type peptide coupling reagent. Chemistry Letters，1999，(11):1163-1164
[7] Li P，XuJ C. HOBt and HOAt-derived immonium salts: new and highly efficient coupling reagents for peptide synthesis. TetrahedronLetters，2000，41(5):721-724
[8] Li P，Xu J C. The X ray structures of HOBt-based immonium type coupling reagents and the rearrangement of Benzotriazolyl esters of N}protected amino acids or peptides:N-vs0-substituted forms. Journal of the Chemical Society Perkin Transactions II，2001,(1):113-120
[9] Li P，Xu J C. New and highly efficient immonium type peptide coupling reagents:synthesis，mechanism and application. Tetrahedron，2000，56 (26):4437-4445
[10] Li P，Xu J C. Novel immonium type peptide coupling reagent:5-(1 H-benzotriazol-l-yloxy)-3,4-dihydro-l-methyl 2 H-pyrrolium hex-achloroantimonate (BDMP}).Chinese Journal of Chemistry，2000，18(1):85-93
[11] Li P，Xu J C. Highly efficient synthesis of peptides by rational utilization of novel coupling reagents. Chinese Journal of Chemistry，2000,18(4):456-466
[12] Li P，Xu J C. 2-Bromo-l-ethyl pyridinium tetrafluoroborate (BEP):A powerful coupling reagent for N-methylated peptide synthesis.Chemistry Letters，2000, (3):204-205
[13] Li P，Xu J C. 1-Ethyl-2-fluoro pyridinium salt:A highly efficient condensation reagents for sterically hindered peptide synthesis. ChineseChemical Letters，2000，11(5):377-380
[14] Li P，XuJ C. 1-Ethyl-2-halopyridinium salts，highly efficient coupling reagents for hindered peptide synthesis both in solution and the sol-id-p hale. Tetrahedron，2000，56(41):8119-8131
[15] Li P，Xu J C. A novel thiazolium type peptide coupling reagent for hindered amino acids. Tetrahedron Letters，1999，40(47):8301-8304
[16] Li P，XuJ C. Highly efficient synthesis of sterically hindered peptide containing N-methylated amino acid residues using the 1 H-benzimida-wlium salt CMBI. Tetrahedron，2000，56 (51):9949-9955
[17] Li P，Xu J C. Total synthesis of cyclosporin O (Cs0) both in solution and solid phase using novel thiawlium，immonium and pyridiniumtype coupling reagents: BEMT，BDMP and BEP. Journal of Organic Chemistry，2000，65 (10) :2951-2958
/
| 〈 |
|
〉 |
