Absolute Configuration of 4-Chloroisoleucine in Cyclolithistide A: An Antifungal Peptide Lactone Discovered in Marine Lithistid Sponges.

Cyclolithistide A is a peptide lactone isolated from marine lithistid sponges. Its entire structure, including absolute configurations, has been reported except the relative and absolute configurations of its characteristic residue, 4-chloroisoleucine (4-CIle). We synthesized four isomers of 4-CIle from furfural-derived N-Boc imine and propionaldehyde. Analysis of the acid hydrolysate of cyclolithistide A and the synthetic samples of 4-CIle after derivatization with l- and d-FDAA permitted us to propose the absolute configuration of the 4-chloroisoleucine residue in cyclolithistide A as 2S,3R,4R.

Spatial-photonic Ising machine by space-division multiplexing with physically tunable coefficients of a multi-component model.

This paper proposes a space-division multiplexed spatial-photonic Ising machine (SDM-SPIM) that physically calculates the weighted sum of the Ising Hamiltonians for individual components in a multi-component model. Space-division multiplexing enables tuning a set of weight coefficients as an optical parameter and obtaining the desired Ising Hamiltonian at a time. We solved knapsack problems to verify the system's validity, demonstrating that optical parameters impact the search property. We also investigated a new dynamic coefficient search algorithm to enhance search performance. The SDM-SPIM would physically calculate the Hamiltonian and a part of the optimization with an electronics process.

Low-Rank Combinatorial Optimization and Statistical Learning by Spatial Photonic Ising Machine.

The spatial photonic Ising machine (SPIM) [13D. Pierangeli et al., Large-Scale Photonic Ising Machine by Spatial Light Modulation, Phys. Rev. Lett. 122, 213902 (2019).PRLTAO0031-900710.1103/PhysRevLett.122.213902] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. The primitive version of the SPIM, however, can accommodate Ising problems with only rank-one interaction matrices. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, it acquires the learning ability of Boltzmann machines. We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using the model with low-rank interactions. Thus, the proposed model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.

New synthesis of (±)-karanone, an important aroma compound in agarwood.

A concise synthesis of (±)-karanone, an important aroma compound of agarwood, was achieved from a commercially available 3-methylcyclohex-2-enol in 3.5% yield in 11 steps. The two contiguous stereocenters at C4 and C5 were constructed via Ireland-Claisen rearrangement. The allylic oxidation at C8 was successfully performed with the mixture of tert-butyl hydroperoxide (TBHP) and CuI. A precursor of ring-closing metathesis to construct a bicyclic dienone was efficiently synthesized from iodoenone by 1,4-addition and nucleophilic substitution of the vinyl group in one pot.

Complete Biosynthetic Pathway of the Phosphonate Phosphonothrixin: Two Distinct Thiamine Diphosphate-Dependent Enzymes Divide the Work to Form a C-C Bond.

Phosphonates often exhibit biological activities by mimicking the phosphates and carboxylates of biological molecules. The phosphonate phosphonothrixin (PTX), produced by the soil-dwelling bacterium Saccharothrix sp. ST-888, exhibits herbicidal activity. In this study, we propose a complete biosynthetic pathway for PTX by reconstituting its biosynthesis in vitro. Our intensive analysis demonstrated that two dehydrogenases together reduce phosphonopyruvate (PnPy) to 2-hydroxy-3-phosphonopropanoic acid (HPPA) to accelerate the thermodynamically unfavorable rearrangement of phosphoenolpyruvate (PEP) to PnPy. The next four enzymes convert HPPA to (3-hydroxy-2-oxopropyl)phosphonic acid (HOPA). In the final stage of PTX biosynthesis, the "split-gene" transketolase homologue, PtxB5/6, catalyzes the transfer of a two-carbon unit attached to the thiamine diphosphate (TPP) cofactor (provided by the acetohydroxyacid synthase homologue, PtxB7) to HOPA to produce PTX. This study reveals a unique C-C bond formation in which two distinct TPP-dependent enzymes, PtxB5/6 and PtxB7, divide the work to transfer an acetyl group, highlighting an unprecedented biosynthetic strategy for natural products.

Quantitative analysis of nonlinear optical input/output of a quantum-dot network based on the echo state property.

The echo state property, which is related to the dynamics of a neural network excited by input driving signals, is one of the well-known fundamental properties of recurrent neural networks. During the echo state, the neural network reveals an internal memory function that enables it to remember past inputs. Due to the echo state property, the neural network will asymptotically update its condition from the initial condition and is expected to exhibit temporally nonlinear input/output. As a physical neural network, we fabricated a quantum-dot network that is driven by sequential optical-pulse inputs and reveals corresponding outputs, by random dispersion of quantum-dots as its components. In the network, the localized optical energy of excited quantum-dots is allowed to transfer to neighboring quantum-dots, and its stagnation time due to multi-step transfers corresponds to the hold time of the echo state of the network. From the experimental results of photon counting of the fluorescence outputs, we observed nonlinear optical input/output of the quantum-dot network due to its echo state property. Its nonlinearity was quantitatively verified by a correlation analysis. As a result, the relation between the nonlinear input/outputs and the individual compositions of the quantum-dot network was clarified.

Total syntheses of dihydro-ß-agarofuran natural products.

Dihydro-ß-agarofuran (DHßAF) sesquiterpenoids constitute a large family of natural products characterized by a tricyclic architecture comprising trans-decalin and tetrahydrofuran rings, and oxygen functionalities on them. Their pharmacologically and agriculturally important biological properties and intriguing molecular architectures have attracted considerable attention from synthetic organic and medicinal chemists. In 2020, our group achieved a scalable total synthesis of this type of natural product, (-)-isocelorbicol, by developing a highly stereocontrolled protocol, which enabled elaboration to naturally occurring ester derivatives, celafolins B-1, B-2, and B-3. Afterward, the total syntheses of more complex DHßAF sesquiterpenoids, (-)-euonyminol and (-)-euonymine, were reported by 2 research groups via current state-of-the-art methods. This review summarizes the total syntheses of DHßAF natural products from 1979 to 2021.

Enantioselective synthesis of 6-methyloctanal and 8-methyldecanal, the characteristic aroma components in yuzu Citrus junos, and the analysis of their enantiomeric compositions in yuzu essential oil.

6-Methyloctanal and 8-methyldecanal are the characteristic aroma components of yuzu Citrus junos. However, their absolute configurations and enantiomeric compositions in yuzu essential oil have not been analyzed. A concise enantioselective synthesis of both aldehydes was successfully carried out to determine their absolute configurations and enantiomeric compositions. Both aldehydes in yuzu essential oil were found to be (S)-form with high enantiomeric excess.

Synthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells.

A concise synthesis of cajaninstilbene acid was achieved in 7 steps from (E)-3,5-dimethoxystilbene in 8.6% overall yield via the Claisen rearrangement of an aryl reverse-prenyl ether as the key step. Cytotoxic activities against human pancreatic carcinoma PANC-1 cells of cajaninstilbene acid and amorfrutins A-D were also evaluated.

Seven-Step Total Synthesis of Sporothriolide.

An enantioselective total synthesis of sporothriolide, a bioactive furofurandione-type fungal metabolite, has been achieved in a 21% overall yield from a commercially available ß,γ-unsaturated carboxylic acid via seven steps. The key steps of this synthesis include a highly diastereoselective Michael addition of a chiral oxazolidinone derivative to a nitro olefin, the exploitation of an aromatic ring as a masked carboxylic acid functionality, and the base-promoted elimination of nitrous acid to install the α-methylene lactone unit of sporothriolide in the final step.

Homophymamide A, Heterodetic Cyclic Tetrapeptide from a Homophymia sp. Marine Sponge: A Cautionary Note on Configurational Assignment of Peptides That Contain a Ureido Linkage.

A previously unreported heterodetic cyclic peptide, homophymamide A (1), was isolated from a Homophymia sp. marine sponge. The structure of homophymamide A was determined to be a lower homologue of anabaenopeptins by spectroscopic analysis, chemical degradation, and chemical synthesis. Analysis of the acidic hydrolysate showed that the racemization of Lys took place, leading us to pose a cautionary note on the configurational assignment of peptides that contain a ureido bond.

Concise enantioselective synthesis of wine lactone via intramolecular Diels-Alder reaction.

An enantioselective synthesis of (3S,3aS,7aR)-wine lactone, a major aroma component of white wine and citrus juices, was achieved starting from (S)-2-methyl-3-butenoic acid. An intramolecular Diels-Alder reaction was employed as a key step.

Unified synthesis and assessment of tumor cell migration inhibitory activity of optically active UTKO1, originally designed moverastin analog.

UTKO1 is a synthetic analog of a natural tumor cell migration inhibitor, moverastin, isolated from microbial extracts of Aspergillus sp. 7720. UTKO1 was initially developed as a mixture of the stereoisomers. In this study, a concise and unified synthesis of the 4 optically active stereoisomers of UTKO1 was achieved from a known optically pure dihydro-α-ionone through a 5-step sequence. The key transformation in the synthesis was a Nozaki-Hiyama-Kishi (NHK) reaction between an optically active enoltriflate and a known aldehyde to install the chiral allylic hydroxy group at C2'. Simple chromatographic separation of the 2 diastereomers with regard to the allylic hydroxy group was possible by the derivatization into the corresponding acetals with Nemoto's optical resolution reagent, (S)- or (R)-5-allyl-2-oxabicyclo[3.3.0]octene (ALBO). All 4 synthetic stereoisomers of UTKO1 exhibited comparable tumor cell migration inhibitory activity.

Synthesis of a plasmenylethanolamine.

A concise synthesis of a plasmenylethanolamine (PlsEtn-[16:0/18:1 n-9]), known as antioxidative phospholipids commonly found in cell membranes, has been achieved from an optically active known diol through 8 steps. The key transformations for the synthesis of PlsEtn-[16:0/18:1 n-9] are (1) regio- and Z-selective vinyl ether formation via the alkylation of a lithioalkoxy allyl intermediate with an alkyl iodide, and (2) a one-pot phosphite esterification-oxidation sequence to construct the ethanolamine phosphonate moiety in the presence of the vinyl ether functionality. The piperidine salt of synthetic PlsEtn-[16:0/18:1 n-9] was desalinated through reversed-phase high-performance liquid chromatography purification.

Asymmetric synthesis of trans-p-menth-3-ene-1,2,8-triol, the monoterpene isolated from herbal plants.

The monoterpene, trans-p-menth-3-ene-1,2,8-triol, is a naturally occurring alcohol isolated from several herbal plants. In the present work, the asymmetric synthesis of both enantiomers of this natural product was achieved using Sharpless asymmetric dihydroxylation as the key step. A reversal of enantiofacial selectivity was observed in the asymmetric dihydroxylation.

Resolution enhancement in nonlinear interferenceless COACH with point response of subdiffraction limit patterns.

Interferenceless coded aperture correlation holography (I-COACH) is a non-scanning, motionless, incoherent digital holography technique for 3D imaging. The lateral and axial resolutions of I-COACH are equivalent to those of conventional direct imaging with the same numerical aperture. The main component of I-COACH is a coded phase mask (CPM) used as the system aperture. In this study, the CPM has been engineered using a modified Gerchberg-Saxton algorithm to generate a random distribution of subdiffraction spot arrays on the digital camera as a system response to a point source illumination. A library of point object holograms is created to calibrate the system for imaging different lateral sections of a 3D object. An object is placed within the calibrated 3D space and an object hologram is recorded with the same CPM. The various planes of the object are reconstructed by a non-linear cross-correlation between the object hologram and the point object hologram library. A lateral resolution enhancement of about 25% was noted in the case of I-COACH compared to direct imaging.

Synthesis of the N-Acyl Amycolose Moiety of Amycolamicin and Its Methyl Glycosides.

The N-acyl amycolose moiety incorporated in amycolamicin, a broad-spectrum antibacterial natural product produced by soil actinomycetes, and its two anomeric methyl glycosides have been synthesized enantioselectively each in 12 steps from a known methyl ( R)-lactate derivative by exploiting a diastereoselective nucleophilic addition of a p-methoxybenzyloxy-substituted vinyllithium reagent to an α,ß-bisalkoxy ketone intermediate to provide the corresponding tertiary alcohol as a single diastereomer. The three sugar derivatives are known as cytotoxic degradation products of amycolamicin.

Synthesis and Stereochemical Revision of the Aromatic Polyketide NFAT-133.

NFAT-133, isolated from Streptomyces sp., is an immunosuppressive, antidiabetic, and antitrypanosomal aromatic polyketide with three contiguous stereocenters. The first enantioselective total synthesis of the proposed structure of NFAT-133 [(10R,11R,12S)-1] and its C10 epimer [(10S,11R,12S)-1] was achieved from a known aromatic ester (5) by a 10-step sequence that featured chiral auxiliary-directed asymmetric alkylation and the Evans asymmetric aldol reaction as the chirality-inducing steps. The 1H and 13C NMR data as well as the specific rotation value of natural NFAT-133 were not identical to those of the proposed structure, but were in good agreement with those of its C10 epimer. This led us to conclude that the absolute configuration of NFAT-133 should be revised to 10S, 11R, and 12S.

Unified total synthesis of amorfrutins A and C via the Claisen rearrangement.

A concise, unified total synthesis of the two prenylated aromatic polyketides amorfrutins A and C, which exhibit various medicinally important biological profiles such as antimicrobial, PPARγ modulating and quorum sensing inhibitory activities, has been achieved from commercially available 3,5-dimethoxybenzaldehyde in 38% and 10% overall yields through nine and ten steps, respectively. The key transformation for the synthesis of amorfrutin A was the Claisen rearrangement of a mono-O-(1,1-dimethylallyl)resorcinol derivative to install the C3-prenyl substituent, while that for the synthesis of amorfrutin C was the double Claisen rearrangement of a di-O-(1,1-dimethylallyl)resorcinol derivative to introduce the two prenyl groups at the C3 and C5 positions all at once.

First synthesis and absolute configuration of phorbasin H, a diterpene carboxylic acid isolated from the sponge Phorbas gukulensis.

The first synthesis of phorbasin H, a diterpene carboxylic acid isolated from the sponge Phorbas gukulensis, was achieved using 1,4-trans-cyclohexanedimethanol and (S)-citronellal as starting materials. The data collected in this synthesis indicated the absolute configuration of the naturally occurring phorbasin H to be S.