Total Synthesis of Keramaphidin B and Ingenamine by Base-Catalyzed Diels-Alder Reaction Using Dynamic Regioselective Crystallization.

The control of the selectivity is a central issue in the total synthesis of complex natural products. In this paper, we report the total synthesis of (±)-keramaphidin B and (±)-ingenamine. The key reaction is a DMAP-catalyzed Diels-Alder reaction in which the regioselectivity is completely controlled by dynamic crystallization. Our synthesis successfully demonstrates that dynamic crystallization can be an alternative when the selectivity is not controlled by either kinetic or thermodynamic approaches in solution.

Unsupervised learning with a physics-based autoencoder for estimating the thickness and mixing ratio of pigments.

Layered surface objects represented by decorated tomb murals and watercolors are in danger of deterioration and damage. To address these dangers, it is necessary to analyze the pigments' thickness and mixing ratio and record the current status. This paper proposes an unsupervised autoencoder model for thickness and mixing ratio estimation. The input of our autoencoder is spectral data of layered surface objects. Our autoencoder is unique, to our knowledge, in that the decoder part uses a physical model, the Kubelka-Munk model. Since we use the Kubelka-Munk model for the decoder, latent variables in the middle layer can be interpretable as the pigment thickness and mixing ratio. We conducted a quantitative evaluation using synthetic data and confirmed that our autoencoder provides a highly accurate estimation. We measured an object with layered surface pigments for qualitative evaluation and confirmed that our method is valid in an actual environment. We also present the superiority of our unsupervised autoencoder over supervised learning.

Total Synthesis of Paclitaxel.

The total synthesis of paclitaxel (Taxol) is described. Double Rubottom oxidation of the bis(silyl enol ether) derived from a tricarbocyclic diketone effectively installed a bridgehead olefin and C-5/C-13 hydroxy groups in a one-step operation. The novel Ag-promoted oxetane formation smoothly constructed the tetracyclic framework of paclitaxel.

Crystal structure of (+)-(1S,5S,6S,7S,10S,11S,16S)-16-hy-droxy-7-(meth-oxy-meth-oxy)-11,15,18,18-tetra-methyl-3,13-dioxo-2,4-dioxa-tetra-cyclo[12.3.1.01,5.06,11]octa-dec-14-en-10-yl benzoate.

In the fused tetra-cyclic system of the title compound, C29H36O9, the five-membered dioxolane ring adopts a twist conformation; the two adjacent C atoms deviate alternately from the mean plane of the other three atoms by -0.252 (6) and 0.340 (6) Å. The cyclo-hexane, cyclo-hexene and central cyclo-octane rings show chair, half-chair and boat-chair forms, respectively. There are three intra-molecular C-H⋯O inter-actions supporting the mol-ecular conformation, with one S(6) and two S(7) graph-set motifs. In the crystal, inter-molecular O-H⋯O hydrogen bonds connect the mol-ecules into a helical chain running along the c-axis direction, generating a C(7) graph-set motif. The chains are further linked by inter-molecular C-H⋯O inter-actions to construct a three-dimensional network. There is no valid C-H⋯π inter-action.

Unified Total Synthesis of Pentacyclic Stemoamide-type Alkaloids.

The collective synthesis of pentacyclic stemoamide-type alkaloids is recognized as a daunting task despite high demand for a comprehensive biological profiling of these natural products. In this Letter, we report a unified synthesis of seven pentacyclic alkaloids and two unnatural derivatives. The keys to success are (1) the chemoselective assembly of four five-membered building blocks, (2) the direct oxidation of pyrrolidine natural products to pyrrole derivatives, and (3) the stereodivergent construction of totally E- or Z-substituted butenolides.

Asymmetric Total Synthesis of Fasicularin by Chiral N-Alkoxyamide Strategy.

The asymmetric total synthesis of fasicularin is reported. The key to success is the use of a chiral N-alkoxyamide to control both reactivity and stereoselectivity. This functional group enables the aza-spirocyclization and the reductive Strecker reaction, which cannot be realized with an ordinary amide. In addition, use of the chiral alkoxy group establishes two consecutive stereocenters in the aza-spirocyclization through remote stereocontrol.

Crystal structure of (-)-(R,E)-3-(1,3-benzodioxol-5-yl)-5-[(4S,5R)-5-hy-droxy-methyl-2,2-dimethyl-1,3-dioxolan-4-yl]-N,N-di-methyl-pent-4-enamide.

In the title compound, C20H27NO6, the amide moiety is essentially planar, with a maximum deviation of 0.073 (3) Å, and one of the N-methyl groups shows rotational disorder. The five-membered 1,3-dioxolane ring adopts an envelope form, with the C atom bonded to the olefin side chain as the flap, which deviates from the mean plane through the other four atoms by 0.564 (7) Å. The 1,3-dioxole ring fused to the benzene ring adopts a flattened envelope form, with the C atom between the two O atoms as the flap, which deviates from the mean plane through the other four atoms by 0.215 (7) Å. The C-C=C-C olefin moiety is essentially planar and makes a dihedral angle of 87.1 (3)° with the benzene ring. An intra-molecular O-H⋯O hydrogen bond supports the mol-ecular conformation, enclosing an S(11) graph-set motif. In the crystal, inter-molecular C-H⋯O hydrogen bonding links the mol-ecules into a tape running along the b axis. Furthermore, other weak C-H⋯O hydrogen bonds and a C-H⋯π inter-action connect the tapes into a sheet structure parallel to (100).

Crystal structure of (-)-(5R,7R,8S,9R,10S)-8-methyl-7-[(5R)-3-methyl-2-oxooxolan-3-en-5-yl]-1-aza-6-oxatri-cyclo-[8.3.0.05,9]tridecan-13-one monohydrate.

The title compound, C17H23NO4·H2O, is an epimer of the natural tetra-cyclic alkaloid isosaxorumamide which consists of a fused 5-7-5 tricyclic core and a di-hydro-furan-one substituent. The terminal di-hydro-furan ring is essentially planar with a maximum deviation of 0.0273 (14) Šfrom the mean plane and oxolane, azepane and pyrrolidine rings in the tricyclic ring system adopt twist, twist-chair and envelope forms, respectively. In the crystal, the amide and water mol-ecules are linked by O-H⋯O hydrogen bonds, forming a tape structure running along the b-axis direction. The tapes are further connected by C-H⋯O inter-actions into a three-dimensional architecture.

Unified Total Synthesis of Stemoamide-Type Alkaloids by Chemoselective Assembly of Five-Membered Building Blocks.

A unified total synthesis of stemoamide-type alkaloids is reported. Our synthetic approach features the chemoselective convergent assembly of five-membered building blocks via stemoamide as the common precursor to tetracyclic natural products. The synthesis consists of two successive coupling reactions of the three five-membered building blocks. The first coupling reaction is the vinylogous Michael addition/reduction sequence, which enables the gram-scale synthesis of stemoamide. The second coupling reaction is a chemoselective nucleophilic addition to stemoamide. While the lactone-selective nucleophilic addition to stemoamide affords saxorumamide and isosaxorumamide, the lactam-selective reductive nucleophilic addition leads to the formation of stemonine. Both chemoselective nucleophilic additions enable direct modification of stemoamide, resulting in highly concise and efficient total syntheses of the stemoamide-type alkaloids.

Crystal structure of (-)-methyl (R,E)-4-[(2R,4R)-2-amino-2-tri-chloro-methyl-1,3-dioxolan-4-yl]-4-hy-droxy-2-methyl-but-2-enoate.

In the title compound, C10H14Cl3NO5, the five-membered dioxolane ring adopts an envelope conformation with the C atom bonded to the butenoate side chain as the flap. It deviates from the mean plane of the other atoms in the ring by 0.446 (6) Å. In the crystal, mol-ecules are connected by O-H⋯O hydrogen bonds into helical chains running along the b-axis direction. The chains are linked into a sheet structure parallel to (001) by an N-H⋯O hydrogen bond. These classical hydrogen bonds enclose an R44(24) graph-set motif in the sheet structure. Furthermore, a weak inter-molecular C-H⋯Cl inter-action expands the sheet structures into a three-dimensional network.

Crystal structure of (+)-N-[(1R,5S,6S,9S)-5-hydroxy-methyl-3,3,9-trimethyl-8-oxo-2,4,7-trioxabi-cyclo-[4.3.0]nonan-9-yl]acetamide.

In the title compound, C12H19NO6, the six-membered 1,3-dioxane ring adopts a chair-like conformation. The seat of this chair, containing two O atoms, is essentially planar, with a maximum deviation of 0.0021 (12) Å. The five-membered oxolane ring cis-fused to the 1,3-dioxane ring adopts an envelope form. The bridgehead C atom at the flap, which is bonded to the tetra-substituted C atom of the oxolane ring, deviates from the mean plane of other ring atoms by 0.539 (4) Å. In the crystal, classical O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into a sheet structure enclosing an R 4 (4)(24) graph-set motif. Weak inter-molecular C-H⋯O inter-actions support the sheet formation.

Crystal structure of (+)-methyl (E)-3-[(2S,4S,5R)-2-amino-5-hy-droxy-meth-yl-2-tri-chloro-methyl-1,3-dioxolan-4-yl]-2-methyl-prop-2-enoate.

In the title compound, C10H14Cl3NO5, the five-membered dioxolane ring adopts an envelope conformation. The C atom at the flap, which is bonded to the hy-droxy-methyl substituent, deviates from the mean plane of other ring atoms by 0.357 (5) Å. There are two intra-molecular hydrogen bonds (O-H⋯N and N-H⋯O) between the hy-droxy and amino groups, so that O- and N-bound H atoms involved in these hydrogen bonds are each disordered with equal occupancies of 0.50. The methyl 2-methyl-prop-2-enoate substituent also shows a disordered structure over two sets of sites with refined occupancies of 0.482 (5) and 0.518 (5). In the crystal, mol-ecules are connected into a dimer by an O-H⋯O hydrogen bond. The dimers are further linked by N-H⋯O, C-H⋯N and C-H⋯O inter-actions, extending a sheet structure parallel to ([Formula: see text]01).

Crystal structure of (±)-(7RS,8SR)-7-methyl-1,4-dioxa-spiro-[4.5]decane-7,8-diol.

In the title compound, C9H16O4, the five-membered dioxolane ring adopts a twist conformation; two adjacent C atoms deviate alternately from the mean plane of other atoms by -0.297 (4) and 0.288 (4) Å. The spiro-fused cyclo-hexane ring shows a chair form. The hy-droxy group substituted in an axial position makes an intra-molecular O-H⋯O hydrogen bond with one of the O atoms in the cyclic ether, forming an S(6) ring motif. In the crystal, the O-H⋯O hydrogen bond involving the equatorial hy-droxy group connects the mol-ecules into a zigzag chain with a C(5) motif running along the c axis.

Synthesis of Paclitaxel. 1. Synthesis of the ABC Ring of Paclitaxel by SmI2-Mediated Cyclization.

A convergent synthesis of the ABC ring of antitumor natural product paclitaxel (Taxol) is described. SmI2-mediated reductive cyclization of an allylic benzoate possessing an aldehyde function, synthesized from tri-O-acetyl-d-glucal and 1,3-cyclohexanedione, smoothly afforded the highly strained 6-8-6 tricarbocyclic structure in 66% yield.

Synthesis of Paclitaxel. 2. Construction of the ABCD Ring and Formal Synthesis.

A formal synthesis of the antitumor diterpenoid paclitaxel (Taxol) is described. The ABC ring of paclitaxel, synthesized starting from 1,3-cyclohexanedione and tri-O-acetyl-d-glucal by SmI2-mediated cyclization as the key transformation, was successfully converted to Takahashi's tetracyclic oxetane intermediate. A double Chugaev reaction was employed for introduction of the strained bridgehead olefin, and stereoselective formation of the oxetane ring afforded the known synthetic intermediate, completing the formal synthesis of paclitaxel.

Crystal structures of (±)-(1SR,5SR,6SR,7SR,10SR,11SR,13RS,14SR)-13-hy-droxy-7-meth-oxy-meth-oxy-11,15,18,18-tetra-methyl-3-oxo-2,4-dioxa-tetra-cyclo-[12.3.1.0(1,5).0(6,11)]octa-dec-15-en-10-yl benzoate, its 13-epimer and 13-one derivative.

The title compounds, C29H38O8·0.25C5H12, (A), C29H38O8, (B), and C29H36O8, (C), are tetra-cyclic benzoates possessing a taxane skeleton with a fused dioxolane ring as the core structure. In the asymmetric unit of (A), there are two independent benzoate mol-ecules (A and A') and a half mol-ecule of solvent pentane disordered about an inversion center. The mol-ecular conformations of (A), (B) and (C) are similar except for the flexible meth-oxy-meth-oxy group. The cyclo-hexane, cyclo-hexene and central cyclo-octane rings adopt chair, half-chair and chair-chair (extended crown) forms, respectively. The dioxolane rings are essentially planar, while the dioxolane ring of A' is slightly twisted from the mean plane. In the crystal of (A), inter-molecular O-H⋯O, C-H⋯O and C-H⋯π inter-actions link the independent benzoates alternately, forming a chain structure. In the crystals of (B) and (C), mol-ecules are linked through O-H⋯O and C-H⋯π inter-actions, and C-H⋯O hydrogen bonds, respectively, into similar chains. Further, weak inter-molecular C-H⋯O inter-actions connect the chains into a three-dimensional network in (A) and a sheet in (B), whereas no other interactions are observed for (C).

Crystal structure of (±)-(1SR,5SR,6SR,7SR,10SR,11SR,13SR)-13-benz-yloxy-7-meth-oxy-meth-oxy-11,15,18,18-tetra-methyl-3-oxo-2,4-dioxa-tetra-cyclo-[12.3.1.0(1,5).0(6,11)]octa-deca-14,16-dien-10-yl benzoate.

In the title compound, C36H42O8, the dioxolane ring adopts a twist conformation; the two adjacent C atoms deviate alternately from the mean plane of other atoms by -0.287 (5) and 0.174 (5) Å. The cyclo-hexane, cyclo-hexa-diene and central cyclo-octane rings show chair, half-chair and boat-chair forms, respectively. As a result of the strained ring system, the tetra-subsituted olefin in the cyclo-hexa-diene is skewed from an ideal planar structure. In the crystal, C-H⋯O hydrogen bonds connect the mol-ecules into a sheet parallel to (100). The sheets are further linked by other weak C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

Total synthesis of sphingofungin F by orthoamide-type overman rearrangement of an unsaturated ester.

The total synthesis of sphingofungin F through the Overman rearrangement of an unsaturated ester, which is known to be an unsuitable substrate under standard conditions due to the competitive aza-Michael reaction, is described. The developed conditions enabled the ester to be compatible with the original Overman rearrangement, providing quick access to α,α-disubstituted amino acids by minimizing extra protecting group manipulations and redox reactions.

Crystal structure of (±)-(4RS,5RS,7SR)-4-[(1RS,2RS,3RS,6RS)-3-benzo-yloxy-2-(2-hy-droxy-ethyl)-6-meth-oxy-meth-oxy-2-methyl-cyclo-hex-yl]-8,10,10-trimethyl-2-oxo-1,3-dioxa-spiro-[4.5]dec-8-en-7-yl benzoate benzene monosolvate.

In the title compound, C36H44O10·C6H6, the dioxolane ring adopts an envelope conformation with the C atom bonded to the H atom as the flap, while the cyclo-hexene and cyclo-hexane rings are in half-chair and chair conformations, respectively. In the crystal, a pair of O-H⋯O hydrogen bonds with an R 2 (2)(26) graph-set motif connect the benzoate mol-ecules into an inversion dimer. The dimers are linked by a weak C-H⋯O inter-action into a tape structure along [01-1]. The benzene mol-ecule links the tapes through C-H⋯O and C-H⋯π inter-actions, forming a sheet parallel to (100).

Crystal structure of (±)-(5SR,6SR)-6-ethenyl-1-[(RS)-1-phenyl-eth-oxy]-1-aza-spiro-[4.5]decan-2-one.

In the title compound, C19H25NO2, the pyrrolidine ring adopts an envelope form, with the spiro C atom as the flap, while the cyclo-hexane ring shows a chair form. A weak intra-molecular C-H⋯O inter-action supports the mol-ecular conformation, generating an S(6) ring motif. In the crystal, pairs of C-H⋯O inter-actions connect the mol-ecules into inversion dimers with an R 2 (2)(16) ring motif. The dimers are linked by a second pair of C-H⋯O inter-actions, enclosing an R 4 (2)(12) ring motif, into a tape structure along the b axis.