A Tandem Metal Carbene Cyclization−Cycloaddition Approach to the Pseudolaric Acids

Chen, Bin; Ko, Rebecca Y. Y.; Yuen, Mabel S. M.; Cheng, Ke; Chiu, Pauline

doi:10.1021/jo026399m

Cited by 59 publications

(12 citation statements)

References 50 publications

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“…We confirmed that the bromohydrin 20 is reconverted into the starting epoxide 19 upon treatment with a base. Chlorination15 of the bromohydrin 20 and subsequent deprotection of the alcohols protected as MOM ethers afforded the fully functionalized half fragment 21 with a cis tetrahydrofuran ring, as confirmed by the observation of an NOE between the hydrogen atoms indicated in structure 21 .…”

Section: Methodsmentioning

confidence: 75%

Total Synthesis and Determination of the Absolute Configuration of (+)‐Intricatetraol

et al. 2007

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Intricatetraol (1), a member of a family of squalene-derived triterpene polyethers named oxasqualenoids, [1] was isolated from the red alga Laurencia intricata by Suzuki et al. in 1993. A crude fraction containing intricatetraol (1) as the major component exhibited cytotoxic activity against P388 "leukemia cells" with an IC 50 value of 12.5 mg mL À1 .[2] The structural analysis was mainly carried out by NMR spectroscopic methods. Although it was found that the molecule has C 2 symmetry, the cis configuration within the tetrahydrofuran ring, the R configuration at C11 (C14), the relative configurations at C6 and C7 (C18 and C19), C10 and C11 (C14 and C15), and at bromine-bonded C3 (C22) remained to be determined.There are many other types of oxasqualenoids; however, it is often difficult to determine their configurations even by highly advanced spectroscopic methods, especially for the acyclic portions that include stereogenic quaternary carbon centers, such as C6-C7 (C18-C19) and C10-C11 (C14-C15) in 1. These difficulties have prompted attempts to determine the configurations of oxasqualenoids by chemical synthesis. [3] Furthermore, the presence of the vicinal bromochloro functionality in 1 makes the problem of stereochemical assignment even more inaccessible. An enantioselective method for the synthesis of the vicinal bromochloro functionality, [4] which also occurs in the marine polyhalogenated monoterpene halomon (2), a promising anticancer agent, [5] has never been developed. Herein we report the total assignment of the configuration of (+)-intricatetraol (1) as 3 through the first asymmetric total synthesis of this natural product. The synthesis features the enantioselective construction of the vicinal bromochloro functionality through a pathway in which the configuration is secured.Suzuki et al. suggested structure 4, which disregards the configuration at C3 (C22), as a possibility on the basis of the hypothetical biogenesis, [2] and recently we [6] and Ujihara [7] independently confirmed this assignment. Our retrosynthetic analysis of the target compound 4 is depicted in Scheme 1. We envisaged that it would be efficient to dimerize by olefin metathesis the functionalized fragment 5, which represents half of the molecule, because of the C 2 symmetry of the natural product. The R or S configuration at the carbon atom attached to bromine in 5 could be introduced through epoxide chemistry. The desired trihydroxytetrahydrofuran 6 might be constructed by the stereospecific and stereoselective oxacycScheme 1. Retrosynthetic analysis of the target compound 4. AD= asymmetric dihydroxylation, AE = asymmetric epoxidation.[*] Prof.

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Section: Methodsmentioning

confidence: 75%

Total Synthesis and Determination of the Absolute Configuration of (+)‐Intricatetraol

et al. 2007

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“…After having established a concise route to cyclized compound 4 , it was then converted to tricyclic compound 16 through hydrogenation and reductive ring‐opening using SmI 2 (Scheme ) . After silylation of the resulting secondary alcohol 16 , the Takai reaction was used to introduce an exo ‐methylene moiety, affording compound 18 , whereas the Wittig reaction using Ph 3 P=CH 2 did not proceed.…”

Section: Figurementioning

confidence: 99%

“…4-Dimethylaminopyridine( DMAP) was effective, although the reaction time had to be prolonged to 7h (entry 9). [13] After silylation of the resulting secondary alcohol 16,t he Takai reactionw as used to introduce an exo-methylene moiety, [14] affordingc ompound 18,w hereas the Wittig reaction using Ph 3 P=CH 2 did not proceed. Althought he cyclization with triethylamine gave the desired product in 35 %y ield along with a significant amount of byproduct 13,q uinuclidine and DABCO were effective.…”

mentioning

confidence: 99%

“…4-Dimethylaminopyridine( DMAP) was effective, although the reaction time had to be prolonged to 7h (entry 9 After having established ac oncise route to cyclized compound 4,i tw as then converted to tricyclic compound 16 through hydrogenation and reductiver ing-opening using SmI 2 (Scheme 3). [13] After silylation of the resulting secondary alcohol 16,t he Takai reactionw as used to introduce an exo-methylene moiety, [14] affordingc ompound 18,w hereas the Wittig reaction using Ph 3 P=CH 2 did not proceed. The hydroboration of 18 with 9-borabicyclo[3.3.1]nonane (9-BBN)p roceeded stereoselectively to give alcohol 3.A fter an extensive investigation into functionalization of the Er ing, CÀHo xidation using I 2 and PhI(OAc) 2 under light irradiation [15] affordedt etracyclic compound 19.F unctionalizing this complex molecule in ah igh yield with excellent regioselectivity was beneficial to this strategy.T he TBS group of the secondary alcohol on the sevenmembered ring could be selectively removed, because the other siloxy group, which is oriented in thea xial position, is sterically hindered by an angular methylg roup.D ess-Martin oxidation [16] of the resultant alcoholg ave ketone 20 in 75 % overall yield from exo-methylene compound 18.O ur attention then turned to the stereoselective introductiono fa nother one-carbon unit on the Dring.…”

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confidence: 99%

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Concise Construction of the ACDE Ring System of Calyciphylline A Type Alkaloids by a [5+2] Cycloaddition

Nakamura

Kawakami

Tsukano

et al. 2019

Chemistry A European J

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Ac oncise route for construction of the ACDE ring skeleton in calyciphyllineA type alkaloids was developed using an intramolecular [5+ +2] cycloaddition reaction of an oxidopyrylium species bearing at etrasubstituted olefin. Key to the successo ft his reactionw as the combination of acid and base, which accelerated the construction of this skeleton containing as piro ring and vicinal quaternaryc arbon centers. The resultant tricyclicA DE ring compound was converted to an ACDE ring model through CÀHo xidation anda na za-Wittig reaction.

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“…In more recent work, Chiu and co-workers [167,168] have reported an intramolecular 1,3-dipolar cycloaddition approach toward the pseudolaric acids 85, in which the dipolarophile is an unactivated 1,1-disubstituted alkene. Hence, treatment of the diazo ketone 86 with catalytic Rh 2 (OAc) 4 furnished a mixture of tricyclic products 87 and 88 in nearly equal proportions (Scheme 19.13).…”

Section: Natural Product Synthesis and Core Structuresmentioning

confidence: 99%

Rhodium(II)‐Catalyzed 1,3‐Dipolar Cycloaddition Reactions

Savizky¹,

Austin²

2005

Modern Rhodium‐Catalyzed Organic Reactions

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A Tandem Metal Carbene Cyclization−Cycloaddition Approach to the Pseudolaric Acids

Cited by 59 publications

References 50 publications

Total Synthesis and Determination of the Absolute Configuration of (+)‐Intricatetraol

Total Synthesis and Determination of the Absolute Configuration of (+)‐Intricatetraol

Concise Construction of the ACDE Ring System of Calyciphylline A Type Alkaloids by a [5+2] Cycloaddition

Rhodium(II)‐Catalyzed 1,3‐Dipolar Cycloaddition Reactions

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