Enantioselective Total Syntheses of Manginoids A and C and Guignardones A and C

Article abstract of DOI:10.1002/anie.202104182

An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica-gel-promoted semipinacol rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the Suzuki–Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.

Full text of DOI:10.1002/anie.202104182

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Enantioselective Total Syntheses of Manginoids A and C and
Guignardones A and C
Authors: Hongxiang Lou, Yan Zong, Ze-Jun Xu, Rong-Xiu Zhu, Ai-
Hong Su, Xu-Yuan Liu, Ming-Zhu Zhu, Jing-Jing Han, Jiao-
Zhen Zhang, and Yu-Liang Xu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202104182
Link to VoR: https://doi.org/10.1002/anie.202104182

10.1002/anie.202104182
Angewandte Chemie International Edition
COMMUNICATION
Enantioselective Total Syntheses of Manginoids A and C and
Guignardones A and C
Yan Zong, Ze-Jun Xu,* Rong-Xiu Zhu, Ai-Hong Su, Xu-Yuan Liu, Ming-Zhu Zhu, Jing-Jing Han, Jiao-
Zhen Zhang, Yu-Liang Xu and Hong-Xiang Lou*
[a]
[b]
Y. Zong, Dr. Z.-J. Xu, Dr. R.-X. Zhu, A.-H. Su, X.-Y. Liu, M.-Z. Zhu, J.-J. Han, J.-Z. Zhang, Y.-L. Xu and Prof. H.-X. Lou
Department of Natural Products Chemistry, Key Lab of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
E-mail: xuzejun@sdu.edu.cn, louhongxiang@sdu.edu.cn
Dr. R.-X. Zhu School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
Supporting information for this article is given via a link at the end of the document
Abstract: An enantioselective synthetic approach for preparing
manginoids and guignardones, two types of biogenetically related
meroterpenoids, is reported. This bioinspired and divergent synthesis
employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and
cyclodehydration of the common precursor to forge the central ring of
the manginoids and guignardones, respectively, at a late stage. Key
The structural diversification and potent biological activities
render these compounds attractive targets for organic
synthesis.[3] Yang group reported the first asymmetric total
synthesis of ent-guignardone A and B from D-quinic acid in
2020.[3c] Recently, the first total synthesis of (±)-manginoid A (1)
was described by Snyder et al.[3d] Their elegant synthetic strategy
involved challenging Pinacol coupling and bicycle-forming
etherification. Despite these innovative strategies, the asymmetric
synthesis of manginoids has not been achieved, and efforts
directed toward more divergent routes are scarce. Herein, a
bioinspired strategy to achieve the asymmetric total syntheses of
manginoid A, C, guignardone A, and C is described.
synthetic
steps
include
silica-gel-promoted
semipinacol
rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the
Suzuki-Miyaura reaction of vinyl bromide to achieve fragment
coupling. This synthesis protocol enables the asymmetric syntheses
of four fungal meroterpenoids from commercially available materials.
Fungal meroterpenoids are secondary metabolites derived from
hybrid terpenoid biosynthetic pathways, which possess intriguing
architectures and exhibit excellent biological and pharmacological
activities.[1] Manginoids (1-2, Figure 1) and guignardones (3-4)
are two types of biogenetically related meroterpenoids discovered
from fungus Guignardia mangiferae[2a, 2b] Structurally, manginoids
and guignardones contain a highly substituted cyclopentane
moiety and 6-oxabicyclo[3.2.1]octane fragment, which are forged
via C–C and C–O cyclization of the above-mentioned subunits,
respectively. The hyperbeanol family (5-6) is also likely derived
from a similar biosynthetic pathway.[2c, 2d] Notably, these fungal
meroterpenoids exhibit diverse biological activities. Manginoid A
(1) shows potent inhibition of 11β-hydroxysteroid dehydrogenase
type 1 (IC50 = 0.84 μM) [2a] and guignardone compounds show
promising inhibitory activities against Candida albicans.
Scheme 1. Synthetic analysis of manginoids and guignardones.
Biosynthetically, manginoids have been proposed to generate
from 8 via epoxidation and the nucleophilic ring opening of
2c]
epoxide (Figure 1).[2a,
From a chemistry perspective, an
alternative hypothesis involving an oxidative 1,3-dicarbonyl
radical-initiated cyclization is presented (Scheme 1).[4] We
envisioned that the synthetic diversity of these meroterpenoids
could be realized through late-stage bioinspired cyclizations of the
common precursor 8. The 6-oxabicyclo[3.2.1]octane subunit of 8
could be constructed through a key semipinacol rearrangement of
9,[5] which could be accessible by the Suzuki-Miyaura coupling of
10 and 11.[3b, 6]
Figure 1. Representative structures of manginoids and guignardones.
1
This article is protected by copyright. All rights reserved.

10.1002/anie.202104182
Angewandte Chemie International Edition
COMMUNICATION
Scheme 2. Synthesis of all carbon precursor 9. TBHP = tert-butyl hydroperoxide, DET = diethyl tartrate, DCM = dichloromethane, THF = tetrahydrofuran, PPTS =
pyridinium p-toluenesulfonate, KHMDS = potassium bis(trimethylsilyl)amide, NBS = N-bromosuccinimide, MeOTf = methyl trifluoromethanesulfonate, DMPU = 1,3-
dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, APhos = (4-dimethylaminophenyl)di-tert-butylphosphine, TPAP = tetra-n-propylammonium perruthenate, TFA =
trifluoroacetic acid, NMO = N-methylmorpholine oxide.
The synthesis commenced with the preparation of allylic
alcohol 12, which was readily obtained by the Diels–Alder reaction
of propiolic acid methyl ester and subsequent reduction (see
Supporting Information).[7] Allylic alcohol 12 was subjected to
Sharpless asymmetric epoxidation to afford epoxide 13 in 84%
yield and 94% ee.[5e, 8] (Scheme 2). The hydrolysis of epoxide 13
with boiling water mainly produced triol 14 via Payne
rearrangement,[9] and the absolute configuration was determined
by comparison of the X-ray diffraction data of 16.[10]
Iodoetherification of triol 14 generated iodoether 15, and
subsequent protection with dimethoxypropane produced 6-
oxabicyclo[3.2.1]octane 16 with 51% ee, which was further
improved to 78% ee by recrystallization. Some loss of optical
purity could be caused by the direct epoxide opening with water.
Interestingly, when modified Kornblum oxidation (AgBF4/Me2SO)
was employed to convert alkyl iodide 16 into the corresponding
ketone, an unusual skeletal rearrangement of 16 into
oxabicyclo[2.2.2]octane 17 was observed. It was speculated that
the mechanism of this novel oxidation involved an oxiranium ion
intermediate, and 17 was derived from the solvolysis of the
oxiranium ion by attack at the C4 center (Scheme 2).[11] While an
unexpected rearrangement occurred, it was envisioned that if
semipinacol rearrangement was later successfully employed to
reconvert it into oxabicyclo[3.2.1]octane skeleton, compound 17
could still be exploit.
isolated in 30% yield using Romo’s protocol in the presence of
palladium acetate and Aphos.[3b] Next, the ligands and bases
were screened to determine the optimal conditions to improve the
yield of 19 (see Supporting Information for details), and better
results were later obtained using water as an additive.[6] Acetonide
was removed using trifluoroacetic acid to afford diol 20. The
oxidation of the secondary alcohol of 20 to provide ketone 9
presented an unexpected challenge, i.e., attempts using PDC,
DMP, or IBX failed. Finally, treatment of 20 under Ley condition
generated the desired ketone 9.[14]
Thereafter, ketone 17 was efficiently monobrominated by
treatment of the resulting enol triethyl borate with N-
bromosuccinimide after extensive screening of the reaction
conditions (see Supporting Information for details).[12] Upon
treatment with KHMDS/MeOTf, the formed α-monobrominated
ketone 18 was converted into the desired vinyl bromide 11. With
11 in hand, attempts to perform the Suzuki-Miyaura reaction with
known boronic monoester 10 (prepared from (R)-carvone) were
made.[13] Gratifyingly, the anticipated coupling product 19 was
Scheme 3. Total syntheses of (+)-guignardones A (3) and C (4). PPTS =
pyridinium p-toluenesulfonate, TBAF = tetra-n-butylammonium fluoride, THF =
tetrahydrofuran.
2
This article is protected by copyright. All rights reserved.

10.1002/anie.202104182
Angewandte Chemie International Edition
COMMUNICATION
Scheme 4. Total syntheses of (+)-manginoid A (1) and (-)-manginoid C (2) and the transition states of the radical cyclizations calculated at the PCM-UB3LYP-D3/6-
311+g(2d, p)//UB3LYP-D3/6-31g(d) level in ethyl acetate solution. TBSCl = tert-butyldimethylsilyl chloride, TESOTf = triethylsilyl trifluoromethanesulfonate.
Next, pivotal semipinacol rearrangement was investigated.[5]
Various acids or bases to induce this transformation were
evaluated, and we were pleased to find that natural guignardones
A (3) and C (4) could be obtained by adding pyridinium p-
toluenesulfonate (Scheme 3A). This process involved 1,2-allyl
migration and C–O bond formation through semipinacol
rearrangement and cyclodehydration cascade reaction.
Spectroscopy data collected for these two synthetic
meroterpenoids were consistent with those reported in the
literature. [2b] Compound 21 could not be obtained under various
conditions because of competitive cyclodehydration. Upon careful
examination, it was observed that the desired compound 21 was
formed in small amounts during purification by silica gel
oxidation process.[16] Notably, diastereomer C3-epi-7 could not be
isolated using the above reaction conditions. The structures of 7
and 7’ were initially determined using NMR spectroscopy and
later confirmed by 2D NMR spectroscopy of derivative 23. Density
functional theory (DFT) calculations were performed to
understand the excellent diastereoselectivity observed with
substrate 8.[17] DFT calculations showed that the energy barrier of
transition state TS2 leading to C3-epi-7 is a little higher than that
of TS1, indicating that TS2 is not favorable for this radical
cyclization in the ethyl acetate solution.
This auto-oxidation and subsequent radical cyclization of the
enolizable carbonyl compounds show a general reactivity trend in
this type natural product family (e.g., hyperbeanol B, Figure 1),[18]
and it is highly likely that peroxide natural products such as 7 can
be discovered from Guignardia mangiferae. The silylation of the
hydroxyl groups in 23 with triethylsilyl trifluoromethanesulfonate
delivered 24. Hydrogenation of 24 catalyzed by Pd/C generated a
mixture of keto/hemiketal tautomers 25 and 25’ in 75% yield via
reductive O–O bond cleavage.[19] Burgess dehydration of the
mixture of 25 and 25’ and subsequent desilylation with pyridine
hydrofluoride completed the syntheses of manginoids A (1) and C
(2) in 62% yields. The spectroscopic data for these compounds
were consistent with those reported in the literature for the natural
products. [2a]
In summary, we have developed an enantioselective synthetic
approach for two types of biogenetically related meroterpenoids,
manginoids and guignardones, and comprised an additional case
of “step-efficient syntheses”.[20] An oxidative 1,3-dicarbonyl
radical-initiated cyclization and cyclodehydration are employed to
generate the central ring of the manginoids and guignardones,
respectively. The key features of this bioinspired route include a
silica-gel-promoted semipinacol rearrangement to forge the
common 6-oxabicyclo[3.2.1]octane subunit and Csp3-Csp2 Suzuki-
Miyaura coupling of vinyl bromide. The methodologies described
for forging complex molecular architectures can be applied for the
chromatography.
Hence,
this
challenging
semipinacol
rearrangement was ultimately accomplished using silica gel
(Scheme 3B). The structure of 21 was unambiguously confirmed
by X-ray diffraction analysis. It is worth noting that a novel
aromatization-driven Grob fragmentation of
9
proceeded
smoothly by employing n-Bu4NF to generate phenol 22 (Scheme
3C).[15]
Further efforts were then directed toward the bioinspired
oxidative 1,3-dicarbonyl radical-initiated cyclization to afford
manginoids A (1) and C (2) (Scheme 4A). Demethylation of 21
using HCl or acetic acid directly afforded the cyclodehydration
products, guignardones A (3) and C (4). Other reagents for
demethylation, such as LiCl, did not react. Finally, the treatment
of 21 with 2 N KOH (aq) afforded desired 8 (see Supporting
Information for details). Interestingly, after the preparation of 8,
spontaneous decomposition was observed by NMR and visual
analysis after storage. Further experiments involving the
dissolution of enol 21 in ethyl acetate and exposure to sunlight
and air directly yielded a mixture of keto/hemiketal tautomers 7
and 7’ in 26% yield. As Mn(OAc)3 is an effective oxidant for
enolizable carbonyl compounds,[4] excellent yield of 69% was
obtained using a catalytic amount of Mn(OAc)3 in this auto-
3
This article is protected by copyright. All rights reserved.

10.1002/anie.202104182
Angewandte Chemie International Edition
COMMUNICATION
Wiley, Hoboken, 2016, pp.1–34; c) X. M. Zhang, Y. Q. Tu, F. M. Zhang,
Z. H. Chen, S. H. Wang, Chem. Soc. Rev. 2017, 46, 2272. For selected
applications of semipinacol rearrangement, see: d) S. A. Snyder, S. B.
Thomas, A. C. Mayer, S. P. Breazzano, Angew. Chem. 2012, 124, 4156;
Angew. Chem. Int. Ed. 2012, 51, 4080; e) W. Zhang, W. Shao, F. Li, J.
Gong, Z. Yang, Chem. Asian J. 2015, 10, 1874; f) A. Cernijenko, R.
Risgaard, P. S. Baran, J. Am. Chem. Soc. 2016, 138, 9425; g) K.
Nagaraju, D. Ni, D. Ma, Angew. Chem. 2020, 132, 22223; Angew. Chem.
Int. Ed. 2020, 59, 22039; h) S. H. Wang, R. Q. Si, Q. B. Zhang, X. Guo,
T. Ke, X. M. Zhang, F. M. Zhang, Y. Q. Tu, Angew. Chem. 2020, 132,
22138; Angew. Chem. Int. Ed. 2020, 59, 21954.
syntheses of other structurally related fungal meroterpenoids.
Furthermore, owing to the bioinspired characteristics, this work
can provide insights into the biosynthetic pathways of these types
of meroterpenoids.
Acknowledgements
This work was financially supported by the National Key R&D
Program of China (2019YFA0905700), National Major Scientific
and Technological Special Project for New Drugs Development
(2019ZX09301-112), Major Basic Research Program of
Shandong Provincial Natural Science Foundation (ZR2019ZD26),
and National Natural Science Foundation of China (81874293
and 81903505).
[6]
a) N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. 1979, 20, 3437;
b) S. D. Walker, T. E. Barder, J. R. Martinelli, S. L. Buchwald, Angew.
Chem. 2004, 116, 1907; Angew. Chem. Int. Ed. 2004, 43, 1871; c) T. E.
Barder, S. D. Walker, J. R. Martinelli, S. L. Buchwald, J. Am. Chem. Soc.
2005, 127, 4685; For selected applications of Csp3-Csp2 Suzuki-Miyaura
reaction, see: d) D. D. Dixon, J. W. Lockner, Q. Zhou, P. S. Baran, J. Am.
Chem. Soc. 2012, 134, 8432; e) C. P. Ting, G. Xu, X. Zeng, T. J.
Maimone, J. Am. Chem. Soc. 2016, 138, 14868; f) K. Speck, T. Magauer,
Chem. Eur. J. 2017, 23, 1157; g) S. Chu, N. Münster, T. Balan, M. D.
Smith, Angew. Chem. 2016, 128, 14518; Angew. Chem. Int. Ed. 2016,
55, 14306; h) B. P. Pritchett, J. Kikuchi, Y. Numajiri, B. M. Stoltz, Angew.
Chem. 2016, 128, 13727; Angew. Chem. Int. Ed. 2016, 55, 13529; i) X.
Liu, C. Sun, S. Mlynarski, J. P. Morken, Org. Lett. 2018, 20, 1898; j) L.
Gnägi, S. V. Martz, D. Meyer, R. M. Schärer, P. Renaud, Chem. Eur. J.
2019, 25, 11646; k) T. Xie, C. Zheng, K. Chen, H. He, S. Gao, Angew.
Chem. 2020, 132, 4390; Angew. Chem. Int. Ed. 2020, 59, 4360.
a) D. L. Beach, D. L. Garin, L. A. Kaempfe, K. W. Barnett, J. Organomet.
Chem. 1977, 142, 211; b) H. S. I. Chao, G. A. Berchtold, J. Am. Chem.
Soc. 1981, 103, 898.
Conflict of interest
The authors declare no conflict of interest.
Keywords: total synthesis • cyclization • natural products •
meroterpenoid • asymmetric synthesis
[7]
[1]
[2]
a) Y. Matsuda, I. Abe, Nat. Prod. Rep. 2016, 33, 26; b) L. A. M. Murray,
S. M. K. McKinnie, B. S. Moore, J. H. George, Nat. Prod. Rep. 2020, 37,
1334; c) M. Jiang, Z. Wu, L. Liu, S. Chen, Org. Biomol. Chem. 2021, 19,
1644; d) X. Zhang, T. T. Wang, Q. L. Xu, Y. Xiong, L. Zhang, H. Han, K.
Xu, W. J. Guo, Q. Xu, R. X. Tan, H. M. Ge, Angew. Chem. 2018, 130,
8316; Angew. Chem. Int. Ed. 2018, 57, 8184.
[8]
[9]
T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5974.
a) Y. Morimoto, Y. Nishikawa, M. Takaishi, J. Am. Chem. Soc. 2005, 127,
5806; b) Y. Morimoto, T. Okita, H. Kambara, Angew. Chem. 2009, 121,
2576; Angew. Chem. Int. Ed. 2009, 48, 2538.
a) K. Chen, X. Zhang, W. Sun, J. Liu, J. Yang, C. Chen, X. Liu, L. Gao,
J. Wang, H. Li, Z. Luo, Y. Xue, H. Zhu, Y. Zhang, Org. Lett. 2017, 19,
5956; b) W. H. Yuan, M. Liu, N. Jiang, Z. K. Guo, J. Ma, J. Zhang, Y. C.
Song, R. X. Tan, Eur. J. Org. Chem. 2010, 6348; c) Y. R. Li, W. J. Xu, S.
Wei, W. J. Lu, J. Luo, L. Y. Kong, Phytochemistry. 2019, 159, 56; d) Y.
Y. Liu, Z. Ao, Q. Xu, D. R. Zhu, C. Chen, X. B. Wang, J. G. Luo, L. Y.
Kong, Bioorg. Chem. 2019, 87, 409.
[10] Deposition Numbers 2071520 (for 16) and 2071585 (for 21) contain the
supplementary crystallographic data for this paper. These data are
provided free of charge by the joint Cambridge Crystallographic Data
Centre and Fachinformationszentrum Karlsruhe Access Structures
service www.ccdc.cam.ac.uk/structures.
[11] P. A. Bartlett, P. C. Ting, J. Org. Chem. 1986, 51, 2230.
[12] I. Jastrzebska, J. Chem. 2013, 1.
[3]
[4]
a) T. Kobayashi, I. Takizawa, A. Shinobe, Y. Kawamoto, H. Abe, H. Ito,
Org. Lett. 2019, 21, 3008; b) Y. F. Tao, K. Reisenauer, J. H. Taube, D.
Romo, Angew. Chem. 2019, 131, 2760; Angew. Chem. Int. Ed. 2019, 58,
2734; c) Z. Yan, C. Zhao, J. Gong, Z. Yang, Org.Lett. 2020, 22, 1644; d)
Y. A. Zhang, A. Milkovits, V. Agarawal, C. A. Taylor, S. A. Snyder, Angew.
Chem. Int. Ed. 10.1002/anie.202016178.
[13] a) G. Liu, D. Romo, Angew. Chem. 2011, 123, 7679; Angew. Chem. Int.
Ed. 2011, 50, 7537; b) G. Liu, M. E. Shirley, D. Romo, J.Org. Chem. 2012,
77, 2496.
[14] W. P. Griffith, S. V. Ley, G. P. Whitcombe, A. D. White, J. Chem. Soc.,
Chem. Commun., 1987, 1625.
[15]
M. V. Boggiatto, C. S. Heluani, I. J. S. Fenik, C. A. N. Catalán, J.Org.
Chem. 1987, 52, 1505.
For representative examples, see: a) B. B. Snider, Chem. Rev. 1996, 96,
339; b) T. R. R. Pettus, X. T. Chen, S. J. Danishefsky, J. Am. Chem. Soc.
1998, 120, 12684; c) J. Yin, C. Wang, L. Kong, S. Cai, S. Gao, Angew.
Chem. 2012, 124, 7906; Angew. Chem. Int. Ed. 2012, 51, 7786; d) H. P.
Pepper, H. C. Lam, W. M. Bloch, J. H. George, Org. Lett. 2012, 14, 5162;
e) S. He, W. Yang, L. Zhu, G. Du, C. S. Lee, Org. Lett. 2014, 16, 496; f)
C. Daeppen, M. Kaiser, M. Neuburger, K. Gademann, Org. Lett. 2015,
17, 5420; g) Z. Meng, H. Yu, L. Li, W. Tao, H. Chen, M. Wan, P. Yang,
D. J. Edmonds, J. Zhong, A. Li, Nat Commun, 2015, 6, 6096; h) C. Zhu,
Z. Liu, G. Chen, K. Zhang, H. Ding, Angew. Chem. 2015, 127, 893;
Angew. Chem. Int. Ed. 2015, 54, 879; i) S. Yamashita, A. Naruko, Y.
Nakazawa, L. Zhao, Y. Hayashi, M. Hirama, Angew. Chem. 2015, 127,
8658; Angew. Chem. Int. Ed. 2015, 54, 8538; j) R. R. Merchant, K. M.
Oberg, Y. Lin, A. J. E. Novak, J. Felding, P. S. Baran, J. Am. Chem. Soc.
2018, 140, 7462; k) D. Ni, Y. Wei, D. Ma, Angew. Chem. 2018, 130,
10364; Angew. Chem. Int. Ed. 2018, 57, 10207; l) T. Cao, L. Zhu, Y. Lan,
J. Huang, Z. Yang, Org. Lett. 2020, 22, 2517; m) J. Guo, B. Li, W. Ma,
M. Pitchakuntla, Y. Jia, Angew. Chem. 2020, 132, 15307; Angew. Chem.
Int. Ed. 2020, 59, 15195.
[16]
For representative examples of auto-oxidation reaction, see: a) Y. Kita,
K. Higuchi, Y. Yoshida, K. Iio, S. Kitagaki, S. Akai, H. Fujioka, Angew.
Chem. 1999, 111, 731; Angew. Chem. Int. Ed. 1999, 38, 683; b) K. C.
Nicolaou, D. Gray, J. Tae, Angew. Chem. 2001, 113, 3791; Angew.
Chem. Int. Ed. 2001, 40, 3679; c) M. Li, B. Chen, S. Monteiro, A. M.
Rustum, Tetrahedron Lett. 2009, 50, 4575; d) S. J. Mckerrall, L.
Jørgensen, C. A. Kuttruff, F. Ungeheuer, P. S. Baran, J. Am. Chem. Soc.
2014, 136, 5799; e) Z. J. Xu, D. X. Tan, Y. Wu, Org. Lett. 2015, 17, 5092;
f) M. Schmid, D. Trauner, Angew. Chem. 2017, 129, 12500; Angew.
Chem. Int. Ed. 2017, 56, 12332; g) B. C. Cao, G. J. Wu, F, Yu, Y. P. He,
F. S. Han, Org. Lett. 2018, 20, 3687; h) F. M. Miloserdov, M. S. Kirillova,
M. E. Muratore, A. M. Echavarren, J. Am. Chem. Soc. 2018, 140, 5393;
i) H. Ding, A. G. Roberts, R. Chiang, P. G. Harran, J. Org. Chem. 2018,
83, 7231; j) A. Mondal, A. De, S. M. Husain, Org. Lett. 2020, 22, 8511.
[17] M. J. Frisch, et al., In Gaussian, Inc., Wallingford CT, 2009.
[18] When the model studies were conducted, this auto-oxidation reaction was
also occured. (see Supporting Information for details) .
[19] a) K. Igawa, Y. Kawasaki, K. Nishino, N. Mitsuda, K. Tomooka, Chem.
Eur. J. 2014, 20, 9255; b) D. S. Zuckerman, K. A. Woerpel, Tetrahedron,
2019, 75, 4118.
[5] For representative reviews, see: a) Z. L. Song, C. A. Fan, Y. Q. Tu, Chem.
Rev. 2011, 111, 7523; b) A. X. Gao, S. B. Thomas, S. A. Snyder,
Molecular Rearrangements in Organic Synthesis (Ed.: C. M. Rojas),
4
This article is protected by copyright. All rights reserved.

10.1002/anie.202104182
Angewandte Chemie International Edition
COMMUNICATION
[20] For representative reviews, see: a) ) T. Newhouse, P. S. Baran, R. W.
Org. Chem. 2010, 75, 4657; c) J. Schwan, M, Christmann, Chem. Soc.
Rev. 2018, 47, 7985.
Hoffmann, Chem. Soc. Rev. 2009, 38, 3010; b) T. Gaich, P. S. Baran, J.
5
This article is protected by copyright. All rights reserved.

10.1002/anie.202104182
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
Enantioselective total syntheses of fungal meroterpenoids, manginoids A and C, as well as guignardones A and C, are accomplished.
This divergent and bioinspired synthetic strategy involves a Csp3-Csp2 Suzuki-Miyaura coupling of vinyl bromide, silica-gel-promoted
semipinacol rearrangement, and oxidative 1,3-dicarbonyl radical-initiated cyclization.
6
This article is protected by copyright. All rights reserved.