Predictive Analysis of the Side Chain Conformation of the Higher Carbon Sugars: Application to the Preorganization of the Aminoglycoside Ring 1 Side Chain for Binding to the Bacterial Ribosomal Decoding A Site.
Predictive Analysis of the Side Chain Conformation of the Higher Carbon Sugars: Application to the Preorganization of the Aminoglycoside Ring 1 Side Chain for Binding to the Bacterial Ribosomal Decoding A Site.
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DOI：
10.1021/acs.joc.0c01836
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发表时间：
2020-12-18
期刊：
影响因子：
--
通讯作者：
Crich D
中科院分区：
文献类型：
--
作者：
Pirrone MG;Gysin M;Haldimann K;Hobbie SN;Vasella A;Crich D
为了便于预测高碳糖中吡喃糖苷环的环外键，提出了一个模型，该模型将由分支点和两个侧翼中心组成的三个立体中心（醛庚糖和更高的醛庚糖中的C4-C5-C6，唾液酸和乌卢糖酸中的C5-C6-C7）的相对构型与简单开环戊糖的相对构型相关联。通过检查Fischer投影公式，将给定的立体三单元体指定为阿拉伯糖基、lyxo、ribo或xylo，可以通过与已知的简单pepthiols的溶液（在所有情况下=晶体）构象进行比较，预测环外键的构象。在侧链中更远的立体中心，如在N-乙酰神经氨酸的8位，对环外键的构象几乎没有影响。在此基础上，预测了6 ′-同系物4，5-二取代2-脱氧链霉胺类氨基糖苷类抗生素I环中环外键的构象，并通过新合成的衍生物在D_2O中pD_5时的NMR分析得到证实。这些衍生物的抗核糖体和抗菌活性的简要介绍和讨论方面的preorganization的侧链结合到核糖体解码A网站。预计这种预测分析也将用于预测其他2-（1-羟基烷基）-3-羟基四氢吡喃和四氢呋喃中的环外键的构象。
With a view to facilitating prediction of the exocyclic bond to the pyranoside ring in higher carbon sugars a model is advanced that relates the relative configuration of the three stereogenic centers comprised of the branchpoint and of the two flanking centers (C4–C5–C6 in aldoheptoses and higher, and C5–C6–C7 in sialic and ulosonic acids) to that of the simple ring-opened pentoses. Assignment of a given stereotriad as arabino, lyxo, ribo, or xylo by inspection of the Fischer projection formulae permits prediction of conformation of the exocyclic bond by comparison with the known solution (= crystal in all cases) conformations of the simple pentitols. More remote stereogenic centers in the side chain, as in the 8-position of N-acetylneuraminic acid, have little impact on the conformation of the exocyclic bond. On the basis of this model the conformation of the exocyclic bond in ring I of 6’-homologated 4,5-disubstituted 2-deoxystreptamine class aminoglycoside antibiotics was predicted and was borne out by NMR analysis of newly synthesized derivatives in D2O at pD5. The antiribosomal and antibacterial activity of these derivatives is briefly presented and discussed in terms of preorganization of the side chain for binding to the ribosomal decoding A site. It is anticipated that this predictive analysis will also find use in the prediction of the conformation of the exocyclic bonds in other 2-(1-hydroxyalkyl)-3-hydroxytetrahydropyrans and tetrahydrofurans.
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构象锁定的顺式和反式 - 脱叶[4.4.0]单，二 - 二烷糖的修饰；实验限制（3）J（H，H）耦合常数，用于估计碳水化合物侧链种群及其他。
DOI：
10.1021/acs.joc.7b02891
发表时间：
2018-01-19
期刊：
The Journal of organic chemistry
影响因子：
--
作者：
Amarasekara H;Dharuman S;Kato T;Crich D
通讯作者：
Crich D
影响因子：
3.6
作者：
Dhakal, Bibek;Buda, Szymon;Crich, David
通讯作者：
Crich, David
影响因子：
15
作者：
Kancharla PK;Crich D
通讯作者：
Crich D
DOI：
10.1021/acs.joc.8b01459
发表时间：
2018-09-07
期刊：
The Journal of organic chemistry
影响因子：
--
作者：
Dharuman S;Amarasekara H;Crich D
通讯作者：
Crich D
影响因子：
--
作者：
Garneau-Tsodikova S;Labby KJ
通讯作者：
Labby KJ