Total Synthesis of Millingtonine

Brown, Patrick D.; Lawrence, Andrew L.

doi:10.1002/ange.201602869

Cited by 10 publications

(2 citation statements)

References 27 publications

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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%

“…Upon exposure to acidic CDCl3, atrop-abyssomicin C (86) underwent gradual isomerization to abyssomicin C (89), which could by separated by HPLC. During an attempted biomimetic conversion of abyssomicin C (89) into abyssomicin D (88) via conjugate reduction of the enone, followed by intramolecular Michael addition, the authors exclusively isolated a diastereomer named iso-abyssomicin D (91). The latter slowly isomerized into abyssomicin D (88) upon standing in ethanol.…”

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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

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Natural product anticipation through synthesis

2022

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DABCO‐Catalysed [3+2] Cyclization/Deformylation Cascade of p‐Quinols with 3‐Formylchromones: Access to Benzopyrone‐Fused Tetracyclic Ring Systems

et al. 2023

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The construction of benzopyrone‐fused hydrobenzofuranones via DABCO‐catalyzed [3+2] cyclization/deformylation cascade of p‐quinols with 3‐formylchromones is described. The reaction works under mild reaction conditions to provide the desired products in 53–90% yields with complete diastereoselectivities. In addition, an enantioselective version with 81% ee is also realized in the presence of Takemoto's chiral thiourea catalyst.

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Total Synthesis of a Dimeric Thymol Derivative Isolated from Arnica sachalinensis

et al. 2017

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The total synthesis of a dimeric thymol derivative (thymarnicol) isolated from Arnica sachalinensis was accomplished in 6 steps. A key biomimetic Diels–Alder dimerization was found to occur at ambient temperature and the final oxidative cyclization occurs when the substrate is exposed to air and visible light. These results indicate that this natural product is likely the result of spontaneous (non‐enzyme‐mediated) reactivity.

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Total Synthesis of Millingtonine

Cited by 10 publications

References 27 publications

Natural product anticipation through synthesis

Natural product anticipation through synthesis

DABCO‐Catalysed [3+2] Cyclization/Deformylation Cascade of p‐Quinols with 3‐Formylchromones: Access to Benzopyrone‐Fused Tetracyclic Ring Systems

Total Synthesis of a Dimeric Thymol Derivative Isolated from Arnica sachalinensis

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