Total Synthesis of (±)-Mycoepoxydiene, a Novel Fungal Metabolite Having an Oxygen-Bridged Cyclooctadiene Skeleton

Takao, Ken Ichi; Watanabe, Gohshi; Yasui, Hirofumi; Tadano, Kin Ichi

doi:10.1021/ol026338a

Cited by 58 publications

(26 citation statements)

References 19 publications

(16 reference statements)

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“…As structurally related natural product, (ϩ)-mycoepoxydiene (3) was isolated in 1999 [2,3]. We already reported the total syntheses of 1 and 3, which were characterized by a sequential ringopening/cross/ring-closing metathesis strategy [4,5]. Although the stereostructures of 1 and 3 were confirmed by our synthetic studies, the stereochemistry of 2 was not unambiguously established at that time.…”

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confidence: 81%

Total Syntheses of (+)-1893B and Its Three Diastereomers and Evaluation of Their Biological Activities

et al. 2006

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The total syntheses of natural (ϩ)-1893B (2) and three other diastereomers 14, 18, and 21 were accomplished. Starting from the sequential metathesis product 5 prepared in turn from a 7-oxanorbornene derivative (ϩ)-4, 2 was synthesized by means of an epoxyring opening of 9a with trimethylsilylacetylide followed by Wacker-type oxidation of the resulting alkyne 10 for the construction of the g-lactone moiety. By applying the same synthetic sequence, three additional diastereomers of 2, 14, 18, and 21 were also synthesized. The biological activities of previously synthesized 1893A (1), 1893B (2), and the diastereomers of 1893B 14, 18, and 21 were investigated. Introduction1893A (1) and 1893B (2) were isolated in 2003 during the course of antitumor natural products searching from a marine endophytic fungus designated as No. 1893, which exists in mangroves (Fig. 1) [1]. Lin and Chen reported that the extract mixture of No. 1893 appeared to exhibit cytotoxic and insecticidal activities. However, the biological activity of the pure metabolites 1 and 2 has not reported. The structure of 1 was elucidated by extensive spectroscopic studies and finally determined by X-ray crystallographic analysis. As structurally related natural product, (ϩ)-mycoepoxydiene (3) was isolated in 1999 [2,3]. We already reported the total syntheses of 1 and 3, which were characterized by a sequential ringopening/cross/ring-closing metathesis strategy [4,5]. Although the stereostructures of 1 and 3 were confirmed by our synthetic studies, the stereochemistry of 2 was not unambiguously established at that time. Later, we were concerned with the stereochemically defined total synthesis of 2 through the total syntheses of all four possible stereoisomers regarding the vicinal diol moiety in 2. The first total synthesis of natural (ϩ)-2 was reported as a preliminary communication [6]. Herein, we describe in detail the total syntheses of 2 and three additional diastereomers. The evaluation of their biological activities is also presented. Results and DiscussionAccording to our previous report [5], we converted the enantioenriched 7-oxanorbornene derivative (ϩ)-4 (Ͼ95% ee) into the cyclooctadiene 5 through a one-pot ring-expansion metathesis strategy (Scheme 1). The

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confidence: 81%

Total Syntheses of (+)-1893B and Its Three Diastereomers and Evaluation of Their Biological Activities

et al. 2006

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“…Mycoepoxydiene (MED), is composed of a α, β-unsaturated δ-lactone moiety and polyketide backbone with an oxygenbridged cyclooctadiene core . MED has shown anti-microbial, anti-cancer and anti-inflammatory activities (Takao et al, 2002;Lin et al, 2005). MED also helps in reducing bone loss by suppressing receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and NF-κB activation in mice.…”

Section: Marine Fungimentioning

confidence: 99%

Marine Natural Products: New Avenue in Treatment of Osteoporosis

Chaugule¹,

Indap²,

Chiplunkar

2017

Front. Mar. Sci.

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Bone metabolism is a physiological process that maintains the skeletal integrity and bone functions. Skeletal integrity is always balanced by two key cell types-bone resorbing osteoclasts and bone-forming osteoblasts. Imbalance between generation and function of osteoclasts and osteoblasts often leads to pathological conditions such as osteoporosis, osteopetrosis, Paget's disease. Osteoporosis is one of the most common age-related diseases characterized by decreased bone mineral density and microarchitectural deterioration. Current therapies are indeed effective in preventing bone loss but are also followed by side effects. Since many years, marine organisms have been considered as a good source of bioactive molecules or compounds with potential pharmaceutical properties. Marine Natural Products (MNPs) derived from various marine resources such as marine cyanobacteria, dinoflagellates, algae, sponges, soft corals, molluscs, fishes, and mangroves had shown profound effect on bone metabolism through inhibiting osteoclastogenesis and up-regulating osteoblastogenesis via modulating RANK/RANKL/OPG pathway. Amongst the pre-clinically investigated MNPs for management of osteoporosis, very few are under phase I clinical trials. This review discusses the currently available pharmacological drugs and there major health concern in osteoporosis treatment. It further gives an insight into various marine resources and marine-derived bioactive products, depicting their mechanism of action, functional role, and how these can be exploited for the treatment of osteoporosis.

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“…In the total synthesis of (±)-mycoepoxydiene (343), Tadano et al reported the RCM of the diallylated tetrahydrofuran 344 using catalyst [Ru]-I under diluted conditions to prevent oligomerization [91]. A good yield of the desired oxygen-bridged cyclooctene 345 was obtained (83%).…”

Section: Formation Of Eight-membered Carbocycles By Rcmmentioning

confidence: 99%

Synthesis of Natural Products Containing Medium‐Size Carbocycles by Ring‐Closing Alkene Metathesis

Blanchard¹,

Eustache²

2010

Metathesis in Natural Product Synthesis

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Total Synthesis of (±)-Mycoepoxydiene, a Novel Fungal Metabolite Having an Oxygen-Bridged Cyclooctadiene Skeleton

Cited by 58 publications

References 19 publications

Total Syntheses of (+)-1893B and Its Three Diastereomers and Evaluation of Their Biological Activities

Total Syntheses of (+)-1893B and Its Three Diastereomers and Evaluation of Their Biological Activities

Marine Natural Products: New Avenue in Treatment of Osteoporosis

Synthesis of Natural Products Containing Medium‐Size Carbocycles by Ring‐Closing Alkene Metathesis

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