01335nas a2200145 4500008004100000245013200041210006900173260000800242300001400250490000700264520074700271100002101018700002201039856012801061 2019 eng d00a Recent advances in the synthesis of oxaspirolactones and their application in the total synthesis of related natural products 0 aRecent advances in the synthesis of oxaspirolactones and their a cAUG a7270-72920 v173 a

Oxaspirolactones are ubiquitous structural motifs found in natural products and synthetic molecules with a diverse biochemical and physicochemical profile, and represent a valuable target in natural product chemistry and medicinal chemistry. Since the 1970s, numerous innovative synthetic methodologies have been reported for these scaffolds in the context of expanding the range of potential building blocks, catalysts, and modes of transformations (racemic or asymmetric protocols). This review focuses on a broad spectrum of approaches toward the synthesis of oxaspirolactones and their potential application in the total synthesis of biologically relevant natural products starting from the first disclosure to the latest report.

1 aThorat, Sagar, S1 aKontham, Ravindar uhttps://library.ncl.res.in/content/recent-advances-synthesis-oxaspirolactones-and-their-application-total-synthesis-related01462nas a2200205 4500008004100000022001400041245010200055210006900157260000800226300001400234490000700248520074800255100001701003700002201020700001601042700002601058700002201084700002101106856012901127 2022 eng d a0022-326300aReady access to benzannulated [5,5]-oxaspirolactones using Au(III)-catalyzed cascade cyclizations0 aReady access to benzannulated 55oxaspirolactones using AuIIIcata cMAR a3025-30410 v873 a

This work showcases an unprecedented Au(III)-catalyzed cascade cyclization of 2-(4-hydroxyalkynyl)benzoates to access benzannulated [5,5]-oxaspirolactones related to biologically active natural products. This reaction proceeds through an initial 5-endo-dig mode of hydroalkoxylation of the alkynol segment to give the oxocarbenium species (via cyclic enol-ether) followed by the addition of carboxylate onto the oxocarbenium that delivers the oxaspirolactone scaffold. While testing this method's scope, we found that the steric and electronic environment of the hydroxyl group could alter the reaction pathway that delivers isochromenone through a competitive 6-endo-dig mode of attack of the carboxylate onto the tethered alkyne.

1 aMankad, Yash1 aThorat, Sagar, S.1 aDas, Pronay1 aKrishna, Gamidi, Rama1 aKontham, Ravindar1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/ready-access-benzannulated-55-oxaspirolactones-using-auiii-catalyzed-cascade-cyclizations01591nas a2200229 4500008004100000022001400041245014200055210006900197260000800266300001600274490000700290520076700297653001701064653001601081653001501097100002201112700002201134700002501156700002601181700002201207856013201229 2023 eng d a0022-326300aRegioselective synthesis of benzannulated [5,6]-oxaspirolactones via Cu(II)-catalyzed cycloisomerization of 2-(5-Hydroxyalkynyl)benzoates0 aRegioselective synthesis of benzannulated 56oxaspirolactones via cNOV a16915-169330 v883 a

Spiroketals and oxaspirolactones are widely found in biologically active natural products, serving as important structural motifs. In this study, we present a Cu-(II)-catalyzed cascade cycloisomerization of 2-(5-hydroxyalkynyl)-benzoates, enabling the regioselective synthesis of benzannulated [5,6]-oxaspirolactones containing an isochromen-1-one moiety. This strategy offers a rapid and efficient approach to access a diverse array of benzannulated [5,6]-oxaspirolactones. The methodology presented here showcases a broad substrate scope, delivering good yields and scalability up to gram scale. The structures of the oxaspirolactones were unequivocally confirmed through single-crystal X-ray analysis and by analogy using H-1 and C-13-{H-1} NMR data.

10aConstruction10aIsocumarins10aStrategies1 aThorat, Sagar, S.1 aShimpi, Sagar, P.1 aSambherao, Pooja, I.1 aKrishna, Gamidi, Rama1 aKontham, Ravindar uhttps://library.ncl.res.in/content/regioselective-synthesis-benzannulated-56-oxaspirolactones-cuii-catalyzed-cycloisomerization01484nas a2200181 4500008004100000022001400041245012600055210006900181260000800250300001400258490000700272520079700279100002501076700002401101700002601125700002201151856012901173 2024 eng d a1523-706000aReady access to [5,6,5]-Trioxa-spiro and fused ketals via ag-catalyzed cascade annulation of 4-pentyn-1-ols and aldehydes0 aReady access to 565Trioxaspiro and fused ketals via agcatalyzed  cAUG a7116-71210 v263 a

In this study, we unveil the versatility of 4-pentyn-1-ols as carbonyl surrogates for the unprecedented synthesis of diverse oxygen heterocycles, including [5,6,5]-bis-spiroketals (trioxadispiroketals) and [5,6,5]-furano-spiroketals related to bioactive natural products. These reactions commence with the pi-activation-induced intramolecular hydroalkoxylation of 4-pentyn-1-ols, yielding cyclic enol ethers, which undergo subsequent three-component annulation with aldehydes in a [2+2+1+1] fashion, resulting in the formation of [5,6,5]-bis-spiroketals. Notably, the distinctive steric features of alkynyl alcohols, particularly those with a secondary or tertiary alcohol functionality, dictate divergent reaction pathways, leading to the formation of [5,6,5]-furano-spiroketals.

1 aVinodkumar, Ramavath1 aNakate, Ashwini, K.1 aGamidi, Rama, Krishna1 aKontham, Ravindar uhttps://library.ncl.res.in/content/ready-access-565-trioxa-spiro-and-fused-ketals-ag-catalyzed-cascade-annulation-4-pentyn-1