New Synthetic Technology for the Synthesis of Aryl Ethers:  Construction of C-O-D and D-O-E Ring Model Systems of Vancomycin

Nicolaou, K. C.; Boddy, Christopher N.; Natarajan, S.; Yue, Tao; Li, H.; Bräse, Stefan; Ramanjulu, Joshi M.

doi:10.1021/ja9636350

Cited by 139 publications

(67 citation statements)

References 29 publications

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“…This reaction proceeds under mildly Scheme 57. Mechanistic rationale for the triazene-driven bisaryl ether synthesis by Nicolaou et al [254,255] basic conditions in refluxing acetonitrile. The generality and scope of this procedure is demonstrated in Table 4.…”

Section: 199mentioning

confidence: 99%

“…Furthermore, a number of cyclic systems related to the glycopeptide antibiotics were successfully constructed by this method, including the C-O-D (201, Scheme 58) and the D-O-E (203, Scheme 59) ring systems of vancomycin. [254,255] [254,255] [254,255] The triazene-driven bisaryl ether synthesis has several advantages such as the absence of epimerization at sensitive sites and the fertility of the triazene group for further transformations. Thus, replacement of this group with a hydrogen atom, an amine group, a diazonium salt, a phenol, or a halide is possible.…”

Section: 199mentioning

confidence: 99%

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Chemistry, Biology, and Medicine of the Glycopeptide Antibiotics

Nicolaou

Boddy

Bräse³

et al. 1999

Angew. Chem. Int. Ed.

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The war against infectious bacteria is not over! Although vancomycin and glycopeptide antibiotics have provided a strong last line of defence against many drug-resistant bacteria, their overuse has given rise to more dangerous strains of bacteria. An understanding of the chemistry and biology of these highly complex glycopeptides are destined to play a crucial role in the discovery of new antibiotics.

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Section: 199mentioning

confidence: 99%

Section: 199mentioning

confidence: 99%

Chemistry, Biology, and Medicine of the Glycopeptide Antibiotics

Nicolaou

Boddy

Bräse³

et al. 1999

Angew. Chem. Int. Ed.

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728

445

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“…Achieving the first of these objectives required the development of new synthetic methodology because the tests provided by the unique conglomeration of vancomycin's sensitive functional groups (including seven epimerizable arylglycines) and stereochemical complexity (including 18 chiral centers and three axes of atropisomerism) were rather rigorous. Most noteworthy among these discoveries was a triazene-driven aryl ether forming reaction catalyzed by copper salts to generate the two 16-membered macrocyclic rings of the target molecule, a transformation with broad synthetic scope (45)(46)(47)(48)(49). The second task, preparing vancomycin analogs with improved activity, was accomplished by means of an inventive use of a process known as dynamic combinatorial screening (also known as targetdriven combinatorial synthesis).…”

Section: Selected Total Synthesis Endeavorsmentioning

confidence: 99%

The Essence of Total Synthesis

Nicolaou¹,

Snyder²

2005

ChemInform

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For the past century, the total synthesis of natural products has served as the flagship of chemical synthesis and the principal driving force for discovering new chemical reactivity, evaluating physical organic theories, testing the power of existing synthetic methods, and enabling biology and medicine. This perspective article seeks to examine this time-honored and highly demanding art, distilling its essence in an effort to ascertain its power and future potential.Essence (és'ns) n. the most significant part of a thing's nature; the sum of the intrinsic properties without which a thing would cease to be what it is, and which are not affected by accidental modifications. (The New Lexicon Webster's Dictionary) A lthough the practice of total synthesis and the rationale behind its pursuit have changed throughout the course of its history, its most fundamental property has not. At its core, in its most essential form, natural product total synthesis is a vehicle for discovery, one that is perhaps unparalleled by any other endeavor in the realm of chemical synthesis (1-3). The reason follows: every natural product type isolated from the seemingly limitless chemical diversity in nature provides a unique set of research opportunities deriving from its distinctive three-dimensional architecture and biological properties. For instance, in the early part of the 20th century, efforts directed toward the synthesis of the antimalarial agent quinine (1) (Fig. 1) led to a sizeable body of knowledge regarding the construction of heteroaromatic systems and the unique physical properties of quinoline and piperidine rings. In more recent times, its structure has served as the basis for the design of several new classes of antimalarial drugs that have saved thousands of lives (4). Similarly, attempts to construct steroids such as progesterone (2) before World War II provided insights into how carbon-carbon bonds could both be forged and cleaved, with their partial or total synthesis ultimately rendering them available in quantities that are sufficient to propel them into useful drugs, such as the birth control pill, which is now used by millions of women around the world (5). In the 1950s, the highly sensitive ␤-lactam ring of penicillin (3) served as the impetus for John Sheehan (6) to develop carbodiimide-based reagents for the formation of peptide bonds. This discovery capped the first practical synthesis of this essential medicinal agent, enabled the synthesis of designed penicillins with activity profiles superior to the parent natural product, and revolutionized the entire peptidesynthesis field. In the 1960s and 1970s, members of the eicosanoid family of natural products, such as prostaglandin F 2a (4), served as the artistic canvas on which E. J. Corey was inspired to create the first catalysts capable of orchestrating asymmetric Diels-Alder reactions. It also was the arena in which he and his group developed the now ubiquitous family of silyl-based protecting groups, one of the most general and powerful methods for ...

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“…After methylation of shikimic acid 5) and regio-selective protection of trans vicinal diol 3, 5) we performed a stereospecific conversion of the 3-OH of compound 4 with a Mitsunobu reaction. 6,7) The alcohol 4 is treated with triphenylphosphine, diethyl azodicarboxylate (DEAD) and p-nitrobenzoic acid, followed by hydrolyzed with CH 3 ONa, to give the alcohol 5 in 91% yield. 8) As in our former work, before the reduction of methyl ester with diisobutylaluminum hydride (DIBAL-H), there should be an introduction of tert-butyldimethylsilyl (TBDMS) group to increase the stereoselectivity.…”

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confidence: 99%