Total Synthesis of Marinomycins A–C

Nicolaou, K. C.; Nold, Andrea L.; Milburn, Robert R.; Schindler, Corinna S.

doi:10.1002/anie.200601867

Cited by 51 publications

(24 citation statements)

References 20 publications

(14 reference statements)

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“…18 This then underwent deacetylation by K 2 CO 3 in THF/MeOH (1:1) to produce compound 17 . 19 This was then coupled with ( R )-lipoic acid ( 18 ) in the presence of DCC/DMAP to produce NOSH- 4 (Scheme 3). …”

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confidence: 99%

NOSH-Aspirin: A Novel Nitric Oxide–Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

Kodela

Chattopadhyay

Kashfi

2012

ACS Med. Chem. Lett.

152

142

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A series of new hybrids of aspirin (ASA), bearing both nitric oxide (NO) and hydrogen sulfide (H2S)-releasing moieties were synthesized and designated as NOSH compounds (1–4). NOSH-1 (4-(3-thioxo-3H-1,2-dithiol-5-yl) phenyl 2-((4-(nitrooxy)-butanoyl)oxy) benzoate); NOSH-2 (4-(nitrooxy)butyl (2-((4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)carbonyl)phenyl)); NOSH-3 (4-carbamothioylphenyl 2-((4-(nitrooxy)butanoyl)-oxy)benzoate); and NOSH-4 (4-(nitrooxy)butyl 2-(5-((R)-1,2-dithiolan-3-yl)pentanoyloxy)-benzoate). The cell growth inhibitory properties of compounds 1–4 were evaluated in eleven different human cancer cell lines of six different tissue origins. These cell lines are of adenomatous (colon, pancreatic, lung, prostate), epithelial (breast), and lymphocytic (leukemia) origin. All NOSH compounds were extremely effective in inhibiting the growth of these cell lines. NOSH-1 was the most potent, with an IC50 of 48 ± 3 nM in HT-29 colon cancer cells. This is the first NSAID-based compound with such potency. This compound was also devoid of any cellular toxicity, as determined by LDH release. NOSH-1 was comparable to aspirin in its anti-inflammatory properties, using the carrageenan rat paw edema model.

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confidence: 99%

NOSH-Aspirin: A Novel Nitric Oxide–Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

Kodela

Chattopadhyay

Kashfi

2012

ACS Med. Chem. Lett.

152

142

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“…In 2007, we reported the total synthesis of marinomycins A–C and their monomeric versions, monomarinomycin A and isomonomarinomycin A. 198 The total synthesis featured a ketophosphonate-aldehyde coupling and a hydroxyl-directed carbonyl reduction to generate the C-12 to C-27 fragment, which was coupled with the C-1 to C-11 fragment through a Mitsunobu esterification [①] (which was accompanied by configurational inversion of the participating hydroxyl group). These operations were followed by hydroboration [②] and Suzuki coupling [③] to afford the required monomeric unit of the molecule.…”

Section: Highlights Of Contributions From the Author’s Laboratoriesmentioning

confidence: 99%

“…All direct dimerization attempts employing the Suzuki reaction led to a monomeric macrolide species which, upon deprotection with TBAF, furnished a mixture at C-25 and C-27 monomeric lactones, named monomarinomycin A and isomonomarinomycin A. 198,199 Both monomeric marinomycins were found to be devoid of the biological properties of the naturally occurring marinomycin A, underscoring the strict structural requirements of the latter for biological activity. The synthetic challenge posed by marinomycins A-C provided us with the opportunity to explore and compare the scope of a number of popular carbon-carbon bond forming reactions such as the Suzuki, Stille, and Heck cross coupling reactions 118 as well as the olefin metathesis reaction.…”

Section: Highlights Of Contributions From the Author’s Laboratoriesmentioning

confidence: 99%

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

et al. 2012

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The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules—natural and designed—of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products—the organic molecules of nature—is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature’s molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years.

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“…6 Such syntheses, which have largely focused on stereospecificity, can be costly on a large scale. 7,8 For example, the practical total synthesis of discodermolide (Figure 1), a marine polyketide, remains a formidable challenge. We describe the multi-gram, catalytic, asymmetric preparation of stereotriad (1a) by a six-step route that offers convenience and promises further scalability.…”

Section: Introductionmentioning

confidence: 99%

Multi-gram-scale synthesis of a versatile syn-anti stereotriad by a short and cost-effective route

Galler¹,

Bermudez²,

Parker³

2019

Arkivoc

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The polyketide family of natural products includes numerous biologically important molecules that exhibit a variety of complex structures. The biosynthesis of these diverse structures relies on the iterative assembly of individual segments controlled by the enzymes of the polyketide synthase (PKS) family. In the synthesis laboratory, access to stereospecifically-prepared ketide building blocks can be both challenging and costlimiting. We report an efficient, multigram-scale synthesis of the syn-anti synthon (2S,3R,4S)(E)-6-cyclohexyl-3-[(4-methoxybenzyl)oxy]-2,4-dimethylhex-5-en-1-ol from the commercially available cyclohexanecarboxaldehyde in excellent overall yield and purity.

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Total Synthesis of Marinomycins A–C

Cited by 51 publications

References 20 publications

NOSH-Aspirin: A Novel Nitric Oxide–Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

NOSH-Aspirin: A Novel Nitric Oxide–Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

Multi-gram-scale synthesis of a versatile syn-anti stereotriad by a short and cost-effective route

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