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The number of biologically interesting natural products possessing peroxide structure motifs is substantial and still growing. 1 Many peroxy natural products display antitumor, anticancer and anti parasite activities, which are attributed to the propensity of the peroxide to initiate radical reactions in an ironrich environment. 2 Furthermore, peroxide natural products such as artemisinin are clinically important anti malaria drugs. Despite the potential of chiral peroxides as biologically interesting or even clinically important compounds, synthetic methods for the preparation of chiral peroxides are highly limited. 3,4,5,6 In particular efficient catalytic enantioselective peroxidations with simple achiral precursors are urgently needed, yet none are available. In fact only a single example of a chiral auxiliarydirected peroxidation in high diastereoselectivity could be found in the literature. 7 Herein, we wish to report the development of a highly enantioselective peroxidation of α,β-unsaturated ketones with an easily accessible chiral organic catalyst.The base-promoted reaction of α,β-unsaturated ketones 1 with hydroperoxides 2 represents a classic epoxidation reaction. Asymmetric variants of this epoxidation with both chiral metal and organic catalysts have also been reported. 8-13 It is well-established that the epoxide 3 is formed via a two-step mechanism (Scheme 1); nucleophilic addition of the hydroperoxide 2 to 1 followed by an intramolecular nucleophilic substitution of the resulting enolate (5) that breaks the weak peroxide bond. In principle this epoxidation pathway (1 to 3) could be converted into a peroxidation pathway (1 to 6) if 5 could be trapped by protonation, although the overwhelming preference of 5 for the intramolecular nucleophilic substitution is evident from the lack of reported peroxidation of α,β-unsatrated carbonyl compounds.Although chiral amine-catalyzed nucleophilic epoxidations of α,β-unsaturated carbonyl compounds have already been reported, 13 we suspected that a cinchona alkaloid derivative such as 8 14 could not only render the nucleophilic addition of the hydroperoxide 2 to the iminium intermediate 9 enantioselective, but also strongly influence the partitioning of the peroxyenamine intermediate 10 between the epoxidation (10 to 11) and the peroxidation (10 to 12) pathways (Scheme 2). Presumably, due to steric crash and multipoint binding interactions between the peroxyenamine intermediate and the covalently linked cinchona alkaloid, the bond-rotational freedom of the peroxyenamine should be hampered, compared to that of the enolate 5 in Scheme 1. We expected that this conformational rigidity imposed by 8 on the peroxyenamine would diminish its ability to adopt the active conformation by which the nucleophilic enamine moiety is optimally aligned relative to the O-O bond for the nucleophilic attack. This in turn would decelerate the epoxidation. In contrast, with the NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript protonated quinuclidine as a prot...

In EUROCRYPT 2018, Cid et al. [16] introduced a new concept on the cryptographic property of S-boxes: Boomerang Connectivity Table (BCT for short) for evaluating the subtleties of boomerang-style attacks. Very recently, BCT and the boomerang uniformity, the maximum value in BCT, were further studied by Boura and Canteaut [4]. Aiming at providing new insights, we show some new results about BCT and the boomerang uniformity of permutations in terms of theory and experiment in this paper. Firstly, we present an equivalent technique to compute BCT and the boomerang uniformity, which seems to be much simpler than the original definition from [16].

In this communication, we describe an unprecedented highly enantioselective catalytic conjugate addition of simple alkyl thiols to α,β-unsaturated N-acylated oxazolidin-2-ones catalyzed by acidbase bifunctional catalysis. This reaction provides a useful catalytic method for the synthesis of optically active chiral sulfur compounds that are otherwise difficult to prepare by asymmetric catalysis. The successful development of this reaction resulted from a discovery that, upon proper modification, a cinchona alkaloid bearing a thiourea functionality at 6' position can afford highly efficient catalysis for asymmetric conjugate additions.Optically active chiral thiols and sulfides have seen broad applications as biologically interesting compounds, 1 ligands for metallic catalysts, 2 organic catalysts 3 and chiral auxiliaries. 4 The asymmetric conjugate additions with sulfur-nucleophile, or sulfa-Michael additions, constitute a direct and versatile approach towards optically active chiral sulfur compounds. This strategy is particular valuable, since enantioselective nucleophilic additions to carbon-sulfur double bond, unlike those to carbonyls and imines, are not synthetically viable. 5 Accordingly considerable efforts have been devoted to the development of catalytic enantioselective sulfa-Michael reactions.Several effective chiral metallic and organic catalysts have been developed for conjugate additions of aryl thiols to various Michael acceptors. 6 However, the development of effective catalysts for asymmetric sulfa-Michael reactions involving the less active but synthetically E-mail: Deng@brandeis.edu. more useful simple alkyl thiols remains a significant challenge. 7 To date only iminium catalysis by chiral secondary amines has afforded high enantioselectivity for conjugate additions of simple alkyl thiols to α,β-unsaturated aldehydes and ketones. 8 Although providing a significant breakthrough in the asymmetric synthesis of optically active sulfur compounds, due to the sensitive nature of thiols and sulfides toward oxidations, these reactions do not provide straightforward access to valuable chiral sulfur compounds such as β-mercapto acid derivatives, 9 which contain functionalities of higher oxidation state. Currently, such thiol compounds are only accessible by chiral auxiliary-directed conjugate additions. 10 Herein we report the use of acid-base bifunctional catalysts to realize a highly enantioselective sulfaMichael reaction of simple alkyl thiols to α,β-unsaturated N-acylated oxazolidin-2-ones, an α,β-unsaturated carboxylic acid derivative. Being complementary in scope to existing catalytic asymmetric sulfa-Michael reactions of alkyl thiols, this reaction provides a uniquely valuable method for the enantioselective synthesis of chiral sulfur compounds. NIH Public AccessCinchona alkaloids have a venerable history in the development of enantioselective catalytic sulfa-Michael reactions. 11 However, it is until recently that a modified cinchona alkaloid were found to afford useful level of enant...

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The concise collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol has been accomplished in 10-15 steps, with the total synthesis of orientalol E and oxyphyllol being achieved for the first time. The success obtained was enabled by the realization of the [4+3] cycloaddition reaction of 9 and 10. Other features of the synthesis include 1) the intramolecular Heck reaction to access the azulene core, 2) the epoxidation-S(N)2' reduction sequence to access the allylic alcohol, 3) the efficient regioselective and stereoselective formal hydration of the bridging C=C bond in the synthesis of englerins, and 4) the late-stage chemo- and stereoselective C-H oxidation in the synthesis of orientalol E. The total synthesis of these natural products has enabled the structural revision of oxyphyllol and established the absolute stereochemical features of the organocatalytic [4+3] cycloaddition reaction. The identification of 5 as the natural product oxyphyllol, the success in converting 5 to orientalol E, along with the fact that englerins and oxyphyllol were isolated from plants of the same genus Phyllanthus gives support to our proposed biosynthetic pathways. This work may enable detailed biological evaluations of these natural products and their analogues and derivatives, especially of their potential in the fight against renal cell carcinoma (RCC).

Abstract. As two important cryptanalytic methods, impossible differential cryptanalysis and integral cryptanalysis have attracted much attention in recent years. Although relations among other important cryptanalytic approaches have been investigated, the link between these two methods has been missing. The motivation in this paper is to fix this gap and establish links between impossible differential cryptanalysis and integral cryptanalysis.Firstly, by introducing the concept of structure and dual structure, we prove that a → b is an impossible differential of a structure E if and only if it is a zero correlation linear hull of the dual structure E ⊥ . More specifically, constructing a zero correlation linear hull of a Feistel structure with SP -type round function where P is invertible, is equivalent to constructing an impossible differential of the same structure with P T instead of P . Constructing a zero correlation linear hull of an SPN structure is equivalent to constructing an impossible differential of the same structure with (P −1 ) T instead of P . Meanwhile, our proof shows that the automatic search tool presented by Wu and Wang could find all impossible differentials of both Feistel structures with SP -type round functions and SPN structures, which is useful in provable security of block ciphers against impossible differential cryptanalysis.Secondly, by establishing some boolean equations, we show that a zero correlation linear hull always indicates the existence of an integral distinguisher while a special integral implies the existence of a zero correlation linear hull. With this observation we improve the integral distinguishers of Feistel structures by 1 round, build a 24-round integral distinguisher of CAST-256 based on which we propose the best known key recovery attack on reduced round CAST-256 in the non-weak key model, present a 12-round integral distinguisher of SMS4 and an 8-round integral distinguisher of Camellia without F L/F L −1 . Moreover, this result provides a novel way for establishing integral distinguishers and converting known plaintext attacks to chosen plaintext attacks.Finally, we conclude that an r-round impossible differential of E always leads to an r-round integral distinguisher of the dual structure E ⊥ . In the case that E and E ⊥ are linearly equivalent, we derive a direct link between impossible differentials and integral distinguishers of E . Specifically, we obtain that an r-round impossible differential of an SPN structure, which adopts a bit permutation as its linear layer, always indicates the existence of an r-round integral distinguisher. Based on this newly established link, we deduce that impossible differentials of SNAKE(2), PRESENT, PRINCE and ARIA, which are independent of the choices of the S-boxes, always imply the existence of integral distinguishers.Our results could help to classify different cryptanalytic tools. Furthermore, when designing a block cipher, the designers need to demonstrate that the cipher has sufficient security margins against impo...

Cryptanalysis with SAT/SMT, MILP and CP has increased in popularity among symmetric-key cryptanalysts and designers due to its high degree of automation. So far, this approach covers differential, linear, impossible differential, zero-correlation, and integral cryptanalysis. However, the Demirci-Selçuk meet-in-the-middle (DS-MITM) attack is one of the most sophisticated techniques that has not been automated with this approach. By an in-depth study of Derbez and Fouque's work on DS-MITM analysis with dedicated search algorithms, we identify the crux of the problem and present a method for automatic DS-MITM attack based on general constraint programming, which allows the cryptanalysts to state the problem at a high level without having to say how it should be solved. Our method is not only able to enumerate distinguishers but can also partly automate the key-recovery process. This approach makes the DS-MITM cryptanalysis more straightforward and easier to follow, since the resolution of the problem is delegated to offthe-shelf constraint solvers and therefore decoupled from its formulation. We apply the method to SKINNY, TWINE, and LBlock, and we get the currently known best DS-MITM attacks on these ciphers. Moreover, to demonstrate the usefulness of our tool for the block cipher designers, we exhaustively evaluate the security of 8! = 40320 versions of LBlock instantiated with different words permutations in the F functions. It turns out that the permutation used in the original LBlock is one of the 64 permutations showing the strongest resistance against the DS-MITM attack. The whole process is accomplished on a PC in less than 2 hours. The same process is applied to TWINE, and similar results are obtained.