Total synthesis of calicheamicin .gamma.1I. 3. The final stages

Nicolaou, K. C.; Hummel, C. W.; Nakada, Masahisa; Shibayama, K.; Pitsinos, Emmanuel N.; Saimoto, Hiroyuki; Mizuno, Yukio; Baldenius, Kai; Smith, Adrian L.

doi:10.1021/ja00070a006

Cited by 137 publications

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“…In addition to the total synthesis of calicheamicin γ 1 I (Figure 12),35 a number of other notable discoveries were made during this campaign. Thus, a general method was developed based on the Ramberg–Bäcklund reaction for the synthesis of cyclic enediynes,36 many of which were made and studied (Figure 13).…”

Section: Calicheamicin γ1imentioning

confidence: 94%

Inspirations, Discoveries, and Future Perspectives in Total Synthesis

Nicolaou

2009

J. Org. Chem.

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The last one hundred years have witnessed a dramatic increase in the power and reach of total synthesis. The pantheon of accomplishments in the field includes the total synthesis of molecules of unimaginable beauty and diversity such as the four discussed in this article: endiandric acids (1982), calicheamicin γ 1 I (1992), Taxol ® (1994), and brevetoxin B (1995). Chosen from the collection of the molecules synthesized in the author's laboratories, these structures are but a small fraction of the myriad constructed in laboratories around the world over the last century. Their stories, and the background on which they were based, should serve to trace the evolution of the art of chemical synthesis to its present sharp condition, an emergence that occurred as a result of new theories and mechanistic insights, new reactions, new reagents and catalysts, and new synthetic technologies and strategies. Indeed, the advent of chemical synthesis as a whole must be considered as one of the most influential developments of the twentieth century in terms of its impact on society.

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Section: Calicheamicin γ1imentioning

confidence: 94%

Inspirations, Discoveries, and Future Perspectives in Total Synthesis

Nicolaou

2009

J. Org. Chem.

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“…The aryltetrasaccharide of calicheamicin was obtained by total synthesis as described (12,17). The synthesis of the head-to-head dimer of this compound has also been reported (18).…”

Section: Methodsmentioning

confidence: 99%

Sequence-selective carbohydrate-DNA interaction: dimeric and monomeric forms of the calicheamicin oligosaccharide interfere with transcription factor function.

Liu

Smith

Ajito

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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The synthetic oligosaccharide moiety of the antibiotic calicheamicin and the head-to-head dimer of this oligosaccharide are known to bind to the minor groove of DNA in a sequence-selective manner preferring distinct target sequences. We tested these carbohydrates for their ability to interfere with transcription factor function. The The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.carbohydrates can interfere with the sequence-specific binding of transcription factors to DNA and with the activation of transcription. We find that the dimer of the calicheamicin oligosaccharide is a much more effective inhibitor of biological activity than is the monomer. MATERIALS AND METHODSCalicheamicin Carbohydrates. The aryltetrasaccharide of calicheamicin was obtained by total synthesis as described (12,17). The synthesis of the head-to-head dimer of this compound has also been reported (18). Structure and purity of the carbohydrates were verified by thin-layer chromatography and IH NMR spectroscopy.Electrophoretic Mobility Shift Assays. The oligonucleotides used in electrophoretic mobility shift assays are shown in Table 1. The AP-1 binding site is derived from the human collagenase gene promoter. It does not contain a TCCT sequence and serves as a control for nonspecific binding of the carbohydrate. In the AP-1(TCCT) and the AP-1(TCCT)2 oligonucleotides, TCCT sequences (doubly underlined in Table 1) were constructed near the AP-1 consensus. The AP-1(TCCT) oligonucleotide contains one TCCT site, five nucleotides 5' to the consensus, and the AP-1(TCCT)2 oligonucleotide contains two TCCT sites, one immediately 5' to the consensus, and a second one six nucleotides upstream. AP-1(DM) contains the optimal dimer DNA binding sequence AGGAAGTCCT im-

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“…As one might expect from the novelty and complexity of the target molecule, our campaign for the total synthesis of calicheamicin γ 1 I ( 2 ),22 completed in 1992, was rich in chemical challenges and discoveries, a few of which are highlighted here. The unusual N-O glycoside linkage within the oligosaccharide domain was constructed through a Mitsunobu reaction23 with hemiacetal 24 (Scheme 3).…”

Section: Calicheamicin γ1imentioning

confidence: 99%

From nature to the laboratory and into the clinic

Nicolaou

Chen

Dalby

2009

Bioorganic & Medicinal Chemistry

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Natural products possess a broad diversity of structure and function, and they provide inspiration for chemistry, biology, and medicine. In this review article, we highlight and place in context our laboratory's total syntheses of, and related studies on, complex secondary metabolites that were clinically important drugs, or have since been developed into useful medicines, namely amphotericin B (1, Figure 1), calicheamicin γ 1 I (2), rapamycin (3), Taxol® (4), the epothilones [e.g. epothilones A (5) and B (6)], and vancomycin (7). We also briefly highlight our research with other selected inspirational natural products possessing interesting biological activities [i.e. dynemicin A (8, Figure 2), uncialamycin (9), eleutherobin (10), sarcodictyin A (11), azaspiracid-1 (12), thiostrepton (13), abyssomicin C (14), platensimycin (15), platencin (16), and palmerolide A (17)].

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Total synthesis of calicheamicin .gamma.1I. 3. The final stages

Cited by 137 publications

References 0 publications

Inspirations, Discoveries, and Future Perspectives in Total Synthesis

Inspirations, Discoveries, and Future Perspectives in Total Synthesis

Sequence-selective carbohydrate-DNA interaction: dimeric and monomeric forms of the calicheamicin oligosaccharide interfere with transcription factor function.

From nature to the laboratory and into the clinic

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