Yutaka Ukaji

Green/red cyanobacteriochromes regulate complementary chromatic acclimation via a protochromic photocycle

Cyanobacteriochromes (CBCRs) are cyanobacterial members of the phytochrome superfamily of photosensors. Like phytochromes, CBCRs convert between two photostates by photoisomerization of a covalently bound linear tetrapyrrole (bilin) chromophore. Although phytochromes are red/far-red sensors, CBCRs exhibit diverse photocycles spanning the visible spectrum and the near-UV (330–680 nm). Two CBCR subfamilies detect near-UV to blue light (330–450 nm) via a “two-Cys photocycle” that couples bilin 15Z/15E photoisomerization with formation or elimination of a second bilin–cysteine adduct. On the other hand, mechanisms for tuning the absorption between the green and red regions of the spectrum have not been elucidated as of yet. CcaS and RcaE are members of a CBCR subfamily that regulates complementary chromatic acclimation, in which cyanobacteria optimize light-harvesting antennae in response to green or red ambient light. CcaS has been shown to undergo a green/red photocycle: reversible photoconversion between a green-absorbing 15Z state (15ZPg) and a red-absorbing 15E state (15EPr). We demonstrate that RcaE from Fremyella diplosiphon undergoes the same photocycle and exhibits light-regulated kinase activity. In both RcaE and CcaS, the bilin chromophore is deprotonated as 15ZPg but protonated as 15EPr. This change of bilin protonation state is modulated by three key residues that are conserved in green/red CBCRs. We therefore designate the photocycle of green/red CBCRs a “protochromic photocycle,” in which the dramatic change from green to red absorption is not induced by initial bilin photoisomerization but by a subsequent change in bilin protonation state.

[5+1] cycloaddition of C,N-cyclic N'-acyl azomethine imines with isocyanides.

A catalyst-free [5 + 1] cycloaddition reaction between isocyanides and C,N-cyclic N-acyl azomethine imines as the isocyanophile leading to novel heterocycles has been developed. These reactions proceeded quickly and cleanly to afford the corresponding imin-1,3,4-oxadiazin-6-one derivatives in high to excellent yields. A wide range of C,N-cyclic N-acyl azomethine imines and isocyanides were applicable to this reaction.

O-silylative Passerini reaction: a new one-pot synthesis of α-siloxyamides.

A new method for the highly effective synthesis of α-siloxyamides is described. The addition of isocyanide to aldehyde proceeded smoothly in the presence of silanol to give the corresponding α-siloxyamides in high yields. A wide range of aldehydes and isocyanides are applicable in this reaction.

Catalytic asymmetric 1,3-dipolar cycloaddition of azomethine imines to allyl alcohol utilizing tartaric acid ester as a chiral auxiliary

The catalytic regio- and enantioselective 1,3-dipolar cycloaddition of azomethine imines to allyl alcohol was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active trans-pyrazolidines with enantioselectivities up to 93% ee. Addition of MgBr 2 was crucial to realize reproducible high enantioselectivity.

One pot synthesis of optically active 4-isoxazolines by asymmetric addition of alkynylzinc reagents to nitrones followed by cyclization

- One pot synthesis of optically active 4-isoxazolines was achieved by asymmetric addition of alkynylzinc reagents to nitrones utilizing di(t-butyl) (R,R)-tartrate as a chiral auxiliary followed by cyclization. By addition of dimethylzinc, the cyclization step was accelerated to afford the corresponding 4-isoxazolines with up to 93% ee. Furthermore, a cyclized zinc intermediate could be trapped with formaldehyde to give the corresponding 2,3,4,5-tetrasubstituted 4-isoxazoline with 85% ee.

Recent progress in a chiral multinucleating system utilizing tartaric acid esters

In order to develop a practical method for the construction of chiral molecules, we have designed a novel chiral reaction system possessing multi-metal centers utilizing tartaric acid ester as a chiral auxiliary. Based on this concept, we have developed an asymmetric 1,3-dipolar cycloaddition reaction of azomethine imines, an asymmetric hetero Diels-Alder reaction of nitroso compounds, an asymmetric Diels-Alder reaction of o-quinodimethanes. Furthermore, an asymmetric nucleophilic addition of alkynylzinc reagents, prepared in situ from dialkylzinc and 1-alkynes, to nitrones was achieved with high level of stereocontrol. In the last case, the addition of methylzinc salt of a product-like racemic hydroxylamine was found to be effective for unprecedented enhancement of enantioselectivity.

Stereoselective Synthesis of (2Z,4E)-2,4-Pentadien-1-ols via Sequential 1,4-Elimination Reaction and [1,2]-Wittig Rearrangement Starting from (E)-4-Alkoxy-2-butenyl Benzoates

The sequential 1,4-elimination reaction of (E)-4-alkoxy-2-butenyl benzoates and [1,2]-Wittig rearrangement gave (2Z,4E)-2,4-pentadien-1-ols stereoselectively. Z-Selective formation of intermediary vinyl ethers, whose stereochemistry was well elucidated by the syn-effect, was achieved by treatment of the 2-butenyl benzoates with KOH in the presence of Pd catalyst. The subsequent [1,2]-Wittg rearrangement by use of n-BuLi proceeded with retention of the stereochemistry of the intermediary vinyl ethers.

Carboxylic Acid Free Novel Isocyanide-Based Reactions

In order to develop a practical method for the construction of drug-like and heterocyclic compounds, we have designed a novel Passerini- or Ugi-type reaction system where a compound (which we write in the general form as Z-X) composed of an electrophilic (Z) and a nucleophilic group (X) could essentially perform the same function as the carboxylic acid. Based on this concept, we have developed the O-silylative Passerini reaction and the borinic acid catalyzed α-addition of isocyanides to aldehydes and water. In addition, we have designed and demonstrated the addition reaction of isocyanides to nitrones in the presence of TMSCl to afford the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxyamides. Furthermore, a novel [5u2009+u20091] cycloaddition of isocyanide was explored with C,N-cyclic N-acyl azomethine imines as a 1,5-dipole via a strategy involving intramolecular trapping of the isocyanide.

A One‐Pot O‐Phosphinative Passerini/Pudovik Reaction: Efficient Synthesis of Highly Functionalized α‐(Phosphinyloxy)amide Derivatives

A one-pot O-phosphinative Passerini/Pudovik reaction has been developed, based on reacting aldehydes, isocyanides, and phosphinic acids followed by the addition of second aldehydes to form the corresponding α-(phosphinyloxy)amide derivatives. This is the first reported instance of a Passerini-type, isocyanide-based multicomponent reaction using a phosphinic acid instead of a carboxylic acid. The nucleophilicity of the phosphinate group allows a subsequent catalytic Pudovik-type reaction, affording the highly functionalized α-(phosphinyloxy)amide derivative in high yield. A wide range of aldehydes and isocyanides are applicable to this reaction.

One‐Pot Stereoselective Synthesis of 2‐Acylaziridines and 2‐Acylpyrrolidines from N‐(Propargylic)hydroxylamines

The stereoselective direct transformation of N-(propargylic)hydroxylamines into cis-2-acylaziridines was achieved by the combined use of AgBF4 and CuCl. Copper salts were found to promote the transformation of the intermediary 4-isoxazolines into 2-acylaziridines and both 3-aryl- and 3-alkyl-substituted 2-acylaziridines could be prepared by using this method. Furthermore, subsequent 1,3-dipolar cycloaddition of azomethine ylides that were generated inu2005situ from the intermediary 2-acylaziridines with maleimides was achieved in a stereoselective one-pot procedure to afford the corresponding 2-acylpyrrolidines, which consisted of an octahydropyrrolo[3,4-c]pyrrole skeleton.