Biosynthetically Inspired Divergent Syntheses of Merocytochalasans

Long, Xinyu; Wu, Hai‐Chen; Ding, Yiming; Qu, Chunlei; Deng, Jun

doi:10.1016/j.chempr.2020.11.010

Cited by 19 publications

(15 citation statements)

References 56 publications

(55 reference statements)

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“…a | iso-epicolactone (92) [75,76] , (+)brevianamide Y (93), [77][78][79] (±)-desoxyisobruceol (94) [80][81][82][83] , and (-)-prehalenaquinone (95) [84] are additional examples for molecules that were synthesized in the laboratory prior to their isolation. b | Cases of anticipated natural products that await isolation from natural sources: 8-epi-isoaplydactone (96), [85] dia-angiopterlactone B (97), [86] biyouyanagin C (98), [87] epi-pycnanthuquinone C (99), [88] 8-epi-homodimericin A (100), [89] intricarene side-product (101), [90] protected dia-millingtonine (102) [91] , diaincargranine B aglycone (103) [92] , diastereomer towards neonectrolides (104) [93] , preuisolactone precursor (105) [94] , nuphar alkaloid isomer (106) [95] , side-product towards (+)-norcembrene 5 (107) [96] , monolomaiviticin A (108) [97] , 2-epilankacyclinol (109) [98] , 3,7-epi-massadine (110) [99] , santarubin S (111) [100] , epiguajadial B (112) [101] , Δ 23,24 -perovskone (113) [102] , epi-pungiolide A (114) [103] , and iso-aspergilasine A (115) [104] . This review cannot be comprehensive since it relies mostly on our own experience in the field of biomimetic natural product synthesis and is limited by difficulties in finding diffuse information in the vast chemical literature.…”

Section: Discussionmentioning

confidence: 99%

Natural product anticipation through synthesis

2022

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Natural product synthesis remains one of the most vibrant and intellectually rewarding areas of chemistry, although the justifications for pursuing it have evolved over time. In the early years, the emphasis lay on structure elucidation and confirmation through synthesis, as exemplified by the celebrated studies on cocaine, morphine, strychnine and chlorophyll. This was followed by a phase where the sheer demonstration that highly complex molecules could be recreated in the laboratory in a rational manner was enough to justify the economic expense and intellectual agonies of a synthesis. Since then, syntheses of natural products have served as platforms for the demonstration of elegant strategies, for inventing new methodology "on the fly", or to demonstrate the usefulness and scope of methods established with simpler molecules. We now add another aspect that we find fascinating, viz. "Natural Product Anticipation". In this review, we survey cases where the synthesis of a compound in the laboratory has preceded its isolation from Nature. The focus of our review lies on examples where this anticipation of a natural product has triggered a successful search or where synthesis and isolation occurred independently. Finally, we highlight cases where such a possibility has been suggested but not yet confirmed, inviting further collaborations between synthetic and natural product chemists. The total synthesis of natural products has always been a major factor in the development of organic chemistry. The reasons for pursuing it have evolved as the field has progressed. In its early history, total synthesis mostly served to confirm the constitution and configuration of readily available natural products. With the advent of X-ray crystallography, NMR spectroscopy, and mass spectrometry, this aspect has become less important, although numerous recent cases exist where the structure of a natural product was settled through total synthesis. [1,2] As a consequence, the emphasis has shifted more toward reaction development and the definition of efficient synthetic strategies. In some cases, the desire to achieve a particular transformation has led to the invention of new reactions or reagents that did not exist before. [3] If a total synthesis is sufficiently efficient, it can also be used to deliver a prized natural product on scale that can otherwise only be procured at great expense or by ignoring environmental concerns. [4] Many other motivations for total synthesis exist, ranging from its value as a training ground for medicinal chemists to the satisfaction that comes with solving the sheer intellectual challenge that it represents. [5,6] In this account, we wish to highlight yet another reason to pursue it: Natural Product Anticipation.In the early days of organic synthesis, there must have been many cases where a compound was prepared in the laboratory and considered "synthetic" that was subsequently identified as a natural product. For instance, Gabriel made aminoacetone (1) in 1893 using his eponymous method. [7,8]...

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Section: Discussionmentioning

confidence: 99%

Natural product anticipation through synthesis

2022

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“…The different oxidation states of the functional groups on the core framework of these pentacyclic cytochalasans has spurred intense efforts to understand their biosynthesis [17] . Inspired by Corey's general methods of synthetic analysis [18] and biosynthetic analysis of the whole family members, we developed a bioinspired structure network analysis [16a] of all these pentacyclic aspochalasans. We anticipate the biosynthetic pathway of pentacyclic aspochalasans might be as follows (Scheme 1): 1) as it has been demonstrated by Trauner, [10b] aspochalasin D ( 1 ) could be converted to aspergillin PZ ( 2 ) through a Brønsted‐acid‐catalyzed stereospecific alkene cyclization and aspergillin PZ ( 2 ) could be further oxidized to render trichoderone B ( 4 ) (path A); 2) After epoxidation of C19–C20 double bond, aspochalasin D ( 1 ) could be converted to aspochalasin H ( 11 ), which could be further converted to flavichalasine C ( 9 ) through an epoxyalkene cyclization (path B); 3) We speculate trichoderone A ( 3 ) and trichodermone ( 5 ) might be synthesized from aspochalasin Z ( 12 ) through alkene cyclization and a series of oxidative fragmentation [12] .…”

Section: Resultsmentioning

confidence: 99%

Bioinspired Network Analysis Enabled Divergent Syntheses and Structure Revision of Pentacyclic Cytochalasans

Ding

et al. 2021

Angewandte Chemie

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We accomplished the divergent total syntheses of ten pentacyclic cytochalasans (aspergillin PZ, trichodermone, trichoderones, flavipesines, and flavichalasines) from a common precursor aspochalasin D and revised the structures of trichoderone B, spicochalasin A, flavichalasine C, aspergilluchalasin based on structure network analysis of the cytochalasans biosynthetic pathways and DFT calculations. The key steps of the syntheses include transannular alkene/epoxyalkene and carbonyl‐ene cyclizations to establish the C/D ring of pentacyclic aspochalasans. Our bioinspired approach to these pentacyclic cytochalasans validate the proposed biosynthetic speculation from a chemical view and provide a platform for the synthesis of more than 400 valuable cytochalasans bearing different macrocycles and amino‐acid residues.

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“…The common pattern of natural product biomimetic synthesis is that a substrate identical (or highly similar) to its counterpart in the biosynthesis undergoes chemical reactions mechanistically similar to the corresponding enzymatic (or sometimes non-enzymatic) reactions in the biosynthesis, in the order defined by the biosynthetic pathway, to give the target molecule. Some advanced patterns have also emerged in the evolution, for instance, a) biomimetic assembly of a complex natural product with multiple natural products as building blocks (A + B + … → Z) [5][6][7] and b) biomimetic construction of a natural product network (B ← A → C → … → Z) [8][9][10] , which significantly enhance the structural complexity and diversity generated by biomimetic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming of the biosynthetic network of Daphniphyllum alkaloids into a chemically synthetic network through generalized biomimetic strategies

Zhang

Lü

Ren

et al. 2022

Preprint

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Biomimetic synthesis is a fundamental approach to the chemical synthesis of natural products, which, due to the intrinsic correlation between the biogenesis and the structure of natural products, offers many advantages. Conventional biomimetic strategies have evolved on a principle featuring “(essentially) the same substrates, similar reactions, and similar pathways”, which defines the pattern of biomimetic synthesis from the structural, mechanistic, and sequential perspectives. In practice, such highly imitative approaches have proved considerably feasible and efficient. However, applicability of this type of approach is also limited by the principle. To enhance the power of biomimetic synthesis, we envision generalized biomimetic strategies focusing on the key bond formation/cleavage sites implied by the biogenesis of natural products, which allow us to take full advantage of altered substrates, reactions, and pathways while retaining the inherent advantages of biomimetic synthesis. In this study, we showcased the utility of generalized biomimetic strategies in the synthesis of fourteen Daphniphyllum alkaloids from the macrodaphniphyllamine, calyciphylline A, daphnilongeranin A, and daphnicyclidin D subfamilies. The biosynthetic network of these alkaloids was reprogrammed into a powerful chemically synthetic network through substrate-, reaction-, and pathway-altering biomimetic strategies.

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Biosynthetically Inspired Divergent Syntheses of Merocytochalasans

Cited by 19 publications

References 56 publications

Natural product anticipation through synthesis

Natural product anticipation through synthesis

Bioinspired Network Analysis Enabled Divergent Syntheses and Structure Revision of Pentacyclic Cytochalasans

Reprogramming of the biosynthetic network of Daphniphyllum alkaloids into a chemically synthetic network through generalized biomimetic strategies

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