Synthesis of Dysoxylactam A Using Iterative Homologation of Boronic Esters

Rogers, Jack; Aggarwal, Varinder K.

doi:10.1002/ajoc.202100413

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…: [ 14 ] –14.1 ( c 0.5, CHCl 3 ); Aggarwal et al . : [ 15 ] –8.0 (c 1.0, CHCl 3 ). 1 H NMR (500 MHz, Chloroform‐ d ) δ : 6.04 (d, J = 8.7 Hz, 1H), 4.81 (d, J = 9.2 Hz, 1H), 4.66 (dt, J = 8.8, 2.9 Hz, 1H), 3.27 (t, J = 7.4 Hz, 1H), 2.40—2.32 (m, 1H), 2.23—2.15 (m, 2H), 1.87 (d, J = 9.8 Hz, 1H), 1.83—1.75 (m, 1H), 1.71 (q, J = 7.0 Hz, 1H), 1.54—1.38 (m, 8H), 1.37—1.06 (m, 9H), 0.98 (dd, J = 6.9, 2.1 Hz, 3H), 0.94—0.84 (m, 15H).…”

Section: Methodsmentioning

confidence: 99%

“…[ 14 ] Quite recently, Aggarwal and coworkers completed the fourth total synthesis of 1 in 11 steps with about 4.9% overall yield by using iterative lithiation‐borylation reactions as the key C—C bond‐forming and stereo controlling steps. [ 15 ] These synthetic efforts demonstrated that the construction of the…”

Section: Background and Originality Contentmentioning

confidence: 99%

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Concise Total Synthesis of Dysoxylactam A and a Simplified Analog

et al. 2022

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Comprehensive Summary A total synthesis of 17‐membered macrocyclolipopeptide dysoxylactam A, a potent agent reversing P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) in cancer cells, was developed from the starting material (S)‐2‐methylbutanal in a linear sequence of 12 steps with 23.2% overall yield. The key steps include proline‐catalyzed asymmetric aldol reaction, Evans aldol reaction and Krische allylation to construct the multiple stereocenters containing fragment, and ring‐closing metathesis to furnish the macrocycle. This total synthesis facilitates the preparation of large amount samples of dysoxylactam A and the side chain simplified derivatives for further biological tests and preliminary structure‐activity relationship exploration.

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Section: Methodsmentioning

confidence: 99%

Section: Background and Originality Contentmentioning

confidence: 99%

Concise Total Synthesis of Dysoxylactam A and a Simplified Analog

et al. 2022

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“…Ozonolysis with spontaneous lactonisation, followed by oxidation (70% over 2 steps) then afforded (+)-invictolide (49, 16% overall, 8 steps longest linear sequence). The strategy was applied to the total synthesis of serricornin (55) (Fig. 5b).…”

Section: Figure 4 Homologation Of Boronic Esters Using Primary Alkyl ...mentioning

confidence: 99%

Lithiation–borylation methodology in the total synthesis of natural products

2022

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Robust synthetic methods which show broad substrate scope are of great utility in the synthesis of complex organic molecules. Within this arena, synthetic methods employing boronic esters are especially useful since they undergo a wide variety of transformations with very high levels of stereoselectivity. In particular, boronic esters can undergo single or multiple homologations using enantioenriched metal carbenoids. The addition of a suitable enantioenriched lithium or magnesium carbenoid to a boronic ester, with subsequent 1,2-migration, gives a homologated boronic ester with high stereocontrol. The process, termed lithiation-borylation, can be iterated allowing a carbon chain to be "grown" one atom at time with remarkable precision. The iterative homologation has been likened to a molecular assembly line and resembles the way nature assembles natural products, e.g. in polyketide synthase machinery. The application of lithiation-borylation chemistry to the synthesis of a broad variety of natural products is discussed in this Review.

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“…Recently, organoboron compounds have shown great promise in the automated synthesis of small molecules with high complexity. Some of the remarkable pioneering contributions from the Suginome, − Aggarwal, − Burke, − Crudden, and Tsuchimoto groups have led to the practical application of iterative coupling in the total synthesis of complex natural products and pharmaceuticals. Suginome and other groups − ,, demonstrated the iterative coupling capabilities of -Bdan (dan: 1,8-diaminonaphthalene) building blocks employing the Suzuki-Miyaura Coupling (SMC) reaction.…”

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confidence: 99%

“…Suginome and other groups − ,, demonstrated the iterative coupling capabilities of -Bdan (dan: 1,8-diaminonaphthalene) building blocks employing the Suzuki-Miyaura Coupling (SMC) reaction. Burke and co-workers pioneered the automated synthesis of several natural products using -B(MIDA) ester (MIDA: N -methyliminodiacetic acid) building blocks under SMC conditions. − The Aggarwal group developed a unique transition metal-free iterative coupling strategy using the lithiation-borylation sequence in a stereocontrolled manner. − …”

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confidence: 99%

Copper-Catalyzed Protoboration of 1,3-Diynes as a Platform for Iterative Functionalization

et al. 2022

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This paper presents the protoboration of 1,3-diynes as a platform for the iterative functionalization of various groups on enynes and dienes. Synthetic approaches to targets with high complexity are directed toward using small, modular building blocks similar to a “Lego” construction using iterative chemistry and automated synthesis. Organoboron compounds are currently in the spotlight for achieving these goals. Here, we report an operationally simple, regioselective protoboration of 1,3-diynes using a mixed diboron reagent and Cu(I)/phosphine catalyst to provide enynylboronates in good yields. Under similar conditions, diprotoboration of 1,3-diynes was also achieved to access bench-stable 1,4-diboryl-1,3-dienes in good yields and regioselectivities. The iterative coupling capabilities of the products have been demonstrated along with other downstream transformations offering a range of value-added skeletons.

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Synthesis of Dysoxylactam A Using Iterative Homologation of Boronic Esters

Cited by 10 publications

References 28 publications

Concise Total Synthesis of Dysoxylactam A and a Simplified Analog

Concise Total Synthesis of Dysoxylactam A and a Simplified Analog

Lithiation–borylation methodology in the total synthesis of natural products

Copper-Catalyzed Protoboration of 1,3-Diynes as a Platform for Iterative Functionalization

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