Synthetic Investigation toward QS-21 Analogues

Zeng, Zhiyong; Liao, Jianchun; Hu, Zhen-Ni; Liu, De-Yong; Zhang, Qingju; Sun, Jiansong

doi:10.1021/acs.orglett.0c03185

Cited by 13 publications

(11 citation statements)

References 44 publications

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“…SSd (2) could be synthesized by modification of the synthetic approach to SSa (1) (Scheme 5). Thus, the configuration of 16-β-OH in 16 was inverted via Dess-Martin oxidation and NaBH 4 reduction, giving SGG (19) in good yield (65%). Selective protection of the primary 23-OH with pivaloyl group provide diol 20 (81%).…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, these saikosaponins are difficult to purify from plants; therefore, in-depth studies have not been carried out on their structure-activity relationship (SAR) and mode of action. Chemical synthesis of saikosaponins is also a challenging task, given the scarce availability of the triterpene aglycones that bear high oxidation state at the D/E rings [16][17][18][19]. Very recently, we disclosed a site-selective C-H hydroxylation reaction at the D/E rings of pentacyclic triterpenoids, thus paving a venue for the synthesis of saikosaponins [18,20].…”

Section: Introductionmentioning

confidence: 99%

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Facile Synthesis of Saikosaponins

Wang

Bian

et al. 2021

Molecules

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Saikosaponin A (SSa) and D (SSd) are typical oleanane-type saponins featuring a unique 13,28-epoxy-ether moiety at D ring of the aglycones, which exhibit a wide range of biological and pharmacological activities. Herein, we report the first synthesis of saikosaponin A/D (1–2) and their natural congeners, including prosaikosaponin F (3), G (4), saikosaponin Y (5), prosaikogenin (6), and clinoposaponin I (7). The present synthesis features ready preparation of the aglycones of high oxidation state from oleanolic acid, regioselective glycosylation to construct the β-(1→3)-linked disaccharide fragment, and efficient gold(I)-catalyzed glycosylation to install the glycans on to the aglycones.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Facile Synthesis of Saikosaponins

Wang

Bian

et al. 2021

Molecules

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“…With glycosyl ortho-alkenylbenzoates as donors, a general protocol for the highly efficient glycosylation of the 3-OH group of quillaic acid has been devised, based on which the preparation of quillaic acid 3-O-glycoside 137, the key intermediate in the semi-synthesis of QS-21 by Gin et al, 57 has been achieved with a high overall yield (Scheme 26). 58 Thus, under the action of a catalytic amount of Au(I), the condensation between trisaccharide ABz donor 133 and quillaic acid derivative acceptor 134 proceeded smoothly, providing -135 as the sole product in 88% yield, despite a C2-branched trisaccharide donor being applied. The obtained excellent -stereoselectivity in the absence of a neighboring-group participation effect was attributed to the rapid in situ epimerization of -133 into -133 in the presence of the Au(I) catalyst, which subsequently underwent an S N 2-like substitution under catalysis with an Au(I) complex to deliver -135 exclusively.…”

Section: Short Review Synthesis 4 Semi-synthesis Of Triterpenoids Via Glycosylation Strategiesmentioning

confidence: 99%

“…56 . 58 Thus, under the effect of catalytic amounts of Au(I), the condensation between trisaccharide ABz donor 133 and quillaic acid derivative acceptor 134 proceeded smoothly, providing β-135 as the sole product in 88% yield although a C2-branched trisaccharide donor was applied. The obtained excellent βstereoselectivity in the absence of neighboring-group participation effect was attributed to the rapid in situ epimerization of β-133 to α-133 in the presence of Au(I) catalyst, which subsequently underwent an SN2-like substitution under the catalysis of Au(I) complex to deliver β-135 exclusively.…”

Section: Additional Ring Introduction Tacticsmentioning

confidence: 99%

Advances in the Semi-Synthesis of Triterpenoids

Liao

Liu

et al. 2021

Synthesis

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Recent achievements in triterpenoid semi-synthesis have been accounted, which were divided into three parts according to the applied strategies, including functionalization strategy, C-skeleton modification strategy, and glycosylation strategy. In the functionalization strategy part, both functional group inter-conversions and new functional group installations on triterpenoid starting materials were included. As for the C-skeleton modification strategy section, the contents were further divided into three parts according to the applied tactics, including C-skeleton rearrangement, ring scission, and extra heterocyclic ring introduction tactics. Meanwhile, in the glycosylation strategy section, conspicuous achievements in semi-synthesis of both natural and artificial triterpene saponins were encompassed. In the whole account, the pivotal transformations that brought about striking chemical structure variations on the triterpenoid starting materials were highlighted, which would provide inspiration to investigators who have been engaged in or are going to enter this area.

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“…Further transformations are feasible to provide a large variety of the PTs, which are otherwise difficult to access. For example, oxidation of the primary C28−OH in 1 – 6 will provide the corresponding acids, [29,30] which can be subjected to glycosylation to provide various natural saponins [1,31–34] . The availability of these PT derivatives shall facilitate in‐depth studies on their biological activities.…”

Section: Figurementioning

confidence: 99%

Facile Synthesis of Oleanane‐type Pentacyclic Triterpenoids Bearing Hydroxy Groups on D/E Rings

2021

Asian J Org Chem

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Pentacyclic triterpenoids (PTs) comprise one of the largest class of natural products; many bear higher oxidation state on the D/E rings and exhibit a wide range of biological activities. Here, we report the chemical synthesis of a series of oleanane-type PTs bearing hydroxy groups on D/E rings from the largely available oleanolic acid by transformations following site-selective CÀ H hydroxylation.Pentacyclic triterpenoids (PTs) occur widely in plants and exhibit significant biological and pharmacological activities, such as antitumor, anti-inflammatory, and antiviral activities. [1][2][3] The major types of natural PTs include oleananes, ursanes, lupanes, and friedelanes, and their structural diversities are greatly augmented by post-modifications on the basic pentacyclic skeletons via enzymatic CÀ H oxidation, and subsequent Oglycosylation, and acylation. [4][5][6] The post-oxidation commonly occurs at C2, C12, C16, C21, C22, and C23. Some representative oleanane-type PTs bearing oxidative modification on D/E rings are listed in Figure 1, including barringtogenol C (3β,16α,21β,22α,28-pentahydroxyolean-12-ene), [7,8] chichipegenin (3β,16β,22α,28-tetrahydroxyolean-12-ene), [9] 3β,22β-dihydroxyolean-12-ene-28-oic acid, [10] machaerinic acid, [11] and 3β,21α-dihydroxyolean-12-ene-28-oic acid. [12] Among them, chichipegenin (1) was originally isolated from Lemaireocereus chichipe of the Cactaceae family, [9] which showed significant anti-inflammatory activities in both 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model and the carrageenan-induced rat paw edema model. [13] The glycosides of machaerinic acid, including enterolosaponin A, exhibited a highly selective cytotoxicity against mouse macrophages. [14] Given the heterogeneous nature of PTs occuring in plants and especially the scarce availability of the PTs with higher oxidation states, it is difficult to purify these biologically promising compounds from natural sources. Thus, effective and general approaches to the synthesis of these PTs from abundant precursors are in demand, so as to facilitate in-depth studies on their structure-activity relationship (SAR) and mode of action. [15,16] Very recently, we disclosed a site-selective CÀ H hydroxylation protocol on the D/E scaffold of PTs, [17] employing modification of Schönecker and Baran's Cu-mediated aerobic oxidation under the direction of chiral transient pyridine-imino groups (Figure 2). [18,19] Thus, starting from the abundant oleanolic acid, we were able to prepare 22α-ol and 16β-ol derivatives 7 and 8 effectively, and thereafter we have managed to synthesize barringtogenol C and a panel of saikosaponins bearing 16β/αÀ OH or 22αÀ OH group. [17,20] Herein, we report the synthesis of chichipeginin (1) and PTs 2-6, where hydroxy groups are further introduced into C15 and C21 on the D/E rings of the oleanane scaffold (Figure 2).The transposition of 22αÀ OH in PT 7 to 21À OH was firstly examined (Scheme 1). Thus, elimination of the 22αÀ OH in 7 was realized with Tf 2 O in the presence o...

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Synthetic Investigation toward QS-21 Analogues

Cited by 13 publications

References 44 publications

Facile Synthesis of Saikosaponins

Facile Synthesis of Saikosaponins

Advances in the Semi-Synthesis of Triterpenoids

Facile Synthesis of Oleanane‐type Pentacyclic Triterpenoids Bearing Hydroxy Groups on D/E Rings

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