Substrate‐Controlled Asymmetric Total Synthesis of (+)‐Microcladallene B with a Bromination Strategy Based on a Nucleophile‐Assisting Leaving Group

Park, Jang-Hyun; Kim, Byungsook; Kim, Hyoungsu; Kim, Sanghee; Kim, Deukjoon

doi:10.1002/anie.200700854

Cited by 46 publications

(38 citation statements)

References 34 publications

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“…Attempts to form the propargyl trisylate 14b directly from ent-2 with inversion of stereochemistry under Mitsunobu conditions were unsuccessful, 19 although Kim and co- workers recently reported a similar reaction. 20 Ultimately, the desired syn diastereomer was secured by subjecting ent-2 and 2b to classic Mitsunobu conditions that afforded propargyl p-nitrobenzoates 15a and 15b, which were separable by flash chromatography (Scheme 4). Treatment of 15b with K2CO3 in MeOH resulted in global deprotection to the isomerically pure propargyl alcohol 16b.…”

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confidence: 99%

First Total Synthesis and Structural Reassignment of (−)-Aplysiallene

Wang

Pagenkopf

2007

Org. Lett.

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The first total synthesis of (-)-aplysiallene has been completed in 16 steps, and features a key sequential Mukaiyama aerobic oxidative cyclization to prepare the fused bis-THF core. The original stereochemical assignment has been revised as shown.Aplysiallene 1 was first isolated in 1985 from the red alga Laurencia okamurai Yamada by Suzuki and Kurosawa. 1 Its intriguing structural features include 1) a unique cis-fused 2,6-dioxabicyclo[3,3,0]octane skeleton consisting of two trans-tetrahydrofuran rings, 2) an unusual (E,E)-bromodiene side chain, and 3) an Rbromoallene 2 appendage. The absolute stereochemistry of 1 was assigned according to its strong negative optical rotation (due to the allene 3 ) and the relative stereochemistry was assigned by NOE correlations and comparison with kumausallene. 4 In 2001, Okamoto also reported the isolation of 1 from the sea hare aplysia kurodai and found it functions as a Na + /K + ATPase inhibitor with IC50 = 0.7 μM. 5 In this communication, we(1) Suzuki, M.; Kurosawa, E. Phytochemistry 1985, 24, 1999-2002 (2) For review on bromoallene natural products, see: HoffmannRöder, A.; Krause, N. Angew. Chem. Int. Ed. 2004, 43, 1196-1216 (3) Lowe, G. report the first asymmetric total synthesis of aplysiallene and provide evidence for its structural revision. 6 It was envisaged that the R-bromoallene substituent could be prepared from the corresponding R-propargyl alcohol 2a, which in turn should be accessible by an antiselective alkynylation between aldehyde 3 and trimethylsilylacetylene. 7 Although we are unaware of precedence for the direct introduction of the bromodiene subunit, a plausible derivation could be from alcohol 4, which would be stereoselectively prepared by sequential oxidative cyclization 8 of the known (R,R)-diol 5.The synthesis began with reaction of (S,S)-diepoxybutane 6 with vinyl magnesium bromide in the presence of CuBr to give the (S,S)-diol ent-5 in 72% yield. Note the stereochemistry of ent-5 is opposite to that required for the reported natural product, so this should in principle lead to a synthesis of ent-1. While the isolated yield of 13b was only 35%, the dienes 13a and 13b were separable by flash chromatography on gram scale, and unwanted 13a can be recycled by ozonolysis followed by a NaBH4 work up to give alcohol ent-4 in 53% yield. In contrast, attempted conversion of 13a directly into 9 by ozonolysis with a PPh3 work up resulted in complete decomposition of 13a.With the bromodiene side chain at hand, deprotection of the silyl ether 13b by treatment with TBAF followed by Swern oxidation afforded the highly labile aldehyde ent-3 (81%, 2 steps), which was used immediately in the following addition step. As expected, alkynylation of ent-3 with the titanium acetylide of trimethylsilylacetylene (generated in situ with nBuLi and ClTi(OiPr)3) gave ent-2 (13) Initial efforts were undertaken to furnish the bromodiene side chain on a model system by a one-step olefination strategy, but such reactions under various conditions consistently gave ...

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confidence: 99%

First Total Synthesis and Structural Reassignment of (−)-Aplysiallene

Wang

Pagenkopf

2007

Org. Lett.

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“…Alternatively and more efficiently, a direct installation of sulfonate with inversion of configuration was demonstrated by Kim and co-workers for the synthesis of microcladallene B ( 39 ). [19] After the diastereoselective reduction of a ynone intermediate 37 under Felkin–Anh control, the invertive trisylation was accomplished under the Mitsunobu conditions. [19,20] Kim and co-workers also revised the structure of (+)-itomanallene A through total synthesis employing the S N 2′ approach.…”

Section: Stereoselective Halogenation Methods and Applications In mentioning

confidence: 99%

Stereoselective Halogenation in Natural Product Synthesis

2016

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At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp3‐hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

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“…These can be roughly divided into four subgroups, namely: (1) those containing one tetrahydrofuran ring ; (2) those containing two isolated tetrahydrofuran rings (730)(731)(732)(733)(734)(735)(736)(737)(738); (3) those containing two fused tetrahydrofuran rings (739)(740)(741)(742)(743)(744)(745)(746)(747)(748)(749)(750)(751)(752)(753)(754)(755)(756)(757); and (4) maneonenes and isomaneonenes containing three tetrahydrofuran rings (758)(759)(760)(761)(762)(763)(764)(765)(766)(767)(768)(769). These can be roughly divided into four subgroups, namely: (1) those containing one tetrahydrofuran ring ; (2) those containing two isolated tetrahydrofuran rings (730)(731)(732)(733)(734)…”

Section: Acetogenins Containing a Five-membered Cyclic Ether (Tetrahymentioning

confidence: 99%

“…The structure of elatenyne (735) attracted the attention of many research groups, who, utilizing chemical and computational methods, finally succeeded in synthesizing the molecule corresponding to the spectroscopic data of the natural product, and revising the proposed structure to that of a 2,2 0 -bis-tetrahydrofuran derivative. Acetogenins containing two fused tetrahydrofuran rings can be differentiated into those with either a 2,6-dioxabicyclo[3.3.0] octane (739)(740)(741)(742)(743)(744)(745)(746)(747)(748)(749)(750)(751)(752) or a 2,5-dioxabicyclo[2.2.1]heptane (753)(754)(755)(756)(757) substructure. A similar revision was made to the structure of laurendecumbenyne B (733), which was established only on the basis of comparison of NMR data with those originally assigned for 735 [612].…”

Section: Acetogenins Containing a Five-membered Cyclic Ether (Tetrahymentioning

confidence: 99%